10-73192563-A-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_173348.2(FAM149B1):c.290A>T(p.Asp97Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000903 in 1,550,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000086 ( 0 hom. )

Consequence

FAM149B1
NM_173348.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.42

Publications

0 publications found

Variant links:

Genes affected

FAM149B1 (HGNC:29162): (family with sequence similarity 149 member B1) Involved in cilium assembly and protein localization to cilium. Predicted to be located in cilium. Implicated in Joubert syndrome. [provided by Alliance of Genome Resources, Apr 2022]

FAM149B1 links:

DNAJC9 (HGNC:19123): (DnaJ heat shock protein family (Hsp40) member C9) Enables chaperone binding activity; heat shock protein binding activity; and histone binding activity. Involved in nucleosome assembly and positive regulation of ATPase activity. Located in several cellular components, including cytosol; extracellular space; and nucleoplasm. Part of chaperone complex. [provided by Alliance of Genome Resources, Apr 2022]

DNAJC9 links:

Y_RNA (HGNC:):

Y_RNA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.793

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM149B1	NM_173348.2 link	c.290A>T	p.Asp97Val	missense_variant	Exon 4 of 14	ENST00000242505.11	NP_775483.1	Q96BN6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FAM149B1	ENST00000242505.11 link	c.290A>T	p.Asp97Val	missense_variant	Exon 4 of 14	5	NM_173348.2	ENSP00000242505.6	Q96BN6-1
FAM149B1	ENST00000372955.7 link	c.110A>T	p.Asp37Val	missense_variant	Exon 2 of 10	1		ENSP00000362046.3	H7BY93
DNAJC9	ENST00000469143.1 link	n.148-8987T>A		intron_variant	Intron 2 of 2	3
Y_RNA	ENST00000362331.1 link	n.-238T>A		upstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000128

AC:

AN:

156408

AF XY:

0.0000243

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000858

AC:

AN:

1398136

Hom.:

Cov.:

AF XY:

0.0000145

AC XY:

AN XY:

689450

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31524

American (AMR)

AF:

0.00

AC:

AN:

35116

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25148

East Asian (EAS)

AF:

0.00

AC:

AN:

35708

South Asian (SAS)

AF:

0.000140

AC:

AN:

78590

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078634

Other (OTH)

AF:

0.0000172

AC:

AN:

58136

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74350

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41456

American (AMR)

AF:

0.00

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.000414

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 27, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.290A>T (p.D97V) alteration is located in exon 4 (coding exon 4) of the FAM149B1 gene. This alteration results from a A to T substitution at nucleotide position 290, causing the aspartic acid (D) at amino acid position 97 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.62

BayesDel_addAF

Uncertain

0.068

BayesDel_noAF

Uncertain

0.11

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.38

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.076

MetaRNN

Pathogenic

0.79

MetaSVM

Benign

-0.31

MutationAssessor

Uncertain

2.7

PhyloP100

6.4

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-6.8

REVEL

Uncertain

0.39

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

0.99

Vest4

0.87

MutPred

0.49

Gain of helix (P = 0.0425);

MVP

0.29

ClinPred

0.96

GERP RS

5.5

Varity_R

0.85

gMVP

0.84

Mutation Taster

=52/48

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

10-73192563-A-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over