Genetic Variant NM_144664.5:c.49C>T (chr11-95789430-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_144664.5(FAM76B):c.49C>T(p.Pro17Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000549 in 1,457,414 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P17L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

FAM76B
NM_144664.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.49

Publications

0 publications found

Variant links:

Genes affected

FAM76B (HGNC:28492): (family with sequence similarity 76 member B) Located in nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

FAM76B links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144664.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM76B	NM_144664.5	MANE Select	c.49C>T	p.Pro17Ser	missense	Exon 1 of 10	NP_653265.3
	FAM76B	NM_001330357.2		c.49C>T	p.Pro17Ser	missense	Exon 1 of 10	NP_001317286.1	F5GX09

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM76B	ENST00000358780.10	TSL:1 MANE Select	c.49C>T	p.Pro17Ser	missense	Exon 1 of 10	ENSP00000351631.5	Q5HYJ3-1
FAM76B	ENST00000398187.6	TSL:1	n.49C>T		non_coding_transcript_exon	Exon 1 of 11	ENSP00000381248.2	Q5HYJ3-3
FAM76B	ENST00000543641.5	TSL:1	n.49C>T		non_coding_transcript_exon	Exon 1 of 12	ENSP00000444087.1	Q5HYJ3-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000843

AC:

AN:

237248

AF XY:

0.00000772

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:

0.0000188

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000549

AC:

AN:

1457414

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

724660

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33366

American (AMR)

AF:

0.00

AC:

AN:

44356

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26024

East Asian (EAS)

AF:

0.00

AC:

AN:

39486

South Asian (SAS)

AF:

0.00

AC:

AN:

85368

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52766

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.00000721

AC:

AN:

1110188

Other (OTH)

AF:

0.00

AC:

AN:

60134

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000166

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.29

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.96

M_CAP

Uncertain

0.18

MetaRNN

Uncertain

0.69

MetaSVM

Uncertain

-0.20

MutationAssessor

Benign

2.0

PhyloP100

7.5

PrimateAI

Pathogenic

0.88

PROVEAN

Pathogenic

-6.0

REVEL

Uncertain

0.42

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.011

Polyphen

1.0

Vest4

0.67

MutPred

0.35

Loss of glycosylation at P17 (P = 0.0583)

MVP

0.77

MPC

0.68

ClinPred

0.99

GERP RS

4.0

PromoterAI

-0.055

Neutral

(source)

Varity_R

0.78

gMVP

0.56

Mutation Taster

=61/39

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over