dbSNP rs12573841: FAM149B1:p.Gly571Arg (chr10-73240981-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_173348.2(FAM149B1):c.1711G>A(p.Gly571Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0753 in 1,499,480 control chromosomes in the GnomAD database, including 6,597 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.082 ( 640 hom., cov: 31)

Exomes 𝑓: 0.075 ( 5957 hom. )

Consequence

FAM149B1
NM_173348.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.52

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035297573).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM149B1	NM_173348.2 link	c.1711G>A	p.Gly571Arg	missense_variant	Exon 14 of 14	ENST00000242505.11	NP_775483.1	Q96BN6-1
DNAJC9	XM_047424908.1 link	c.*726C>T		3_prime_UTR_variant	Exon 5 of 5		XP_047280864.1
DNAJC9	XM_047424909.1 link	c.*45+681C>T		intron_variant	Intron 5 of 5		XP_047280865.1
DNAJC9	XR_007061950.1 link	n.828+681C>T		intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM149B1	ENST00000242505.11 link	c.1711G>A	p.Gly571Arg	missense_variant	Exon 14 of 14	5	NM_173348.2	ENSP00000242505.6		Q96BN6-1

Frequencies

GnomAD3 genomes

AF:

0.0824

AC:

10921

AN:

132606

Hom.:

640

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0954

Gnomad AMI

AF:

0.0932

Gnomad AMR

AF:

0.0653

Gnomad ASJ

AF:

0.0965

Gnomad EAS

AF:

0.342

Gnomad SAS

AF:

0.222

Gnomad FIN

AF:

0.0429

Gnomad MID

AF:

0.0408

Gnomad NFE

AF:

0.0593

Gnomad OTH

AF:

0.0740

GnomAD3 exomes

AF:

0.103

AC:

16091

AN:

156642

Hom.:

1691

AF XY:

0.111

AC XY:

9156

AN XY:

82778

show subpopulations

Gnomad AFR exome

AF:

0.0725

Gnomad AMR exome

AF:

0.0646

Gnomad ASJ exome

AF:

0.100

Gnomad EAS exome

AF:

0.322

Gnomad SAS exome

AF:

0.215

Gnomad FIN exome

AF:

0.0447

Gnomad NFE exome

AF:

0.0596

Gnomad OTH exome

AF:

0.0827

GnomAD4 exome

AF:

0.0746

AC:

102026

AN:

1366826

Hom.:

5957

Cov.:

AF XY:

0.0789

AC XY:

53266

AN XY:

675474

show subpopulations

Gnomad4 AFR exome

AF:

0.0847

Gnomad4 AMR exome

AF:

0.0647

Gnomad4 ASJ exome

AF:

0.0979

Gnomad4 EAS exome

AF:

0.323

Gnomad4 SAS exome

AF:

0.212

Gnomad4 FIN exome

AF:

0.0466

Gnomad4 NFE exome

AF:

0.0577

Gnomad4 OTH exome

AF:

0.0850

GnomAD4 genome

AF:

0.0825

AC:

10941

AN:

132654

Hom.:

640

Cov.:

AF XY:

0.0854

AC XY:

5549

AN XY:

64988

show subpopulations

Gnomad4 AFR

AF:

0.0959

Gnomad4 AMR

AF:

0.0653

Gnomad4 ASJ

AF:

0.0965

Gnomad4 EAS

AF:

0.342

Gnomad4 SAS

AF:

0.221

Gnomad4 FIN

AF:

0.0429

Gnomad4 NFE

AF:

0.0593

Gnomad4 OTH

AF:

0.0774

Alfa

AF:

0.0730

Hom.:

664

Bravo

AF:

0.157

TwinsUK

AF:

0.0547

AC:

203

ALSPAC

AF:

0.0571

AC:

220

ExAC

AF:

0.118

AC:

2876

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.00097

T;.

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.41

T;T

MetaRNN

Benign

0.0035

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.5

N;.

PrimateAI

Benign

0.46

PROVEAN

Benign

3.2

N;N

REVEL

Benign

0.13

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.040

MutPred

0.067

Gain of catalytic residue at G571 (P = 0.0331);.;

ClinPred

0.0090

GERP RS

4.6

Varity_R

0.11

gMVP

0.083

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over