Genetic Variant NM_152660.3:c.19T>C (chr1-27726099-T-C) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_152660.3(FAM76A):c.19T>C(p.Cys7Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FAM76A
NM_152660.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.41

Publications

0 publications found

Variant links:

Genes affected

FAM76A (HGNC:28530): (family with sequence similarity 76 member A) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FAM76A links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.946

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152660.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM76A	NM_152660.3	MANE Select	c.19T>C	p.Cys7Arg	missense	Exon 1 of 9	NP_689873.1	Q8TAV0-1
FAM76A	NM_001143912.2		c.19T>C	p.Cys7Arg	missense	Exon 1 of 10	NP_001137384.1	Q8TAV0-3
FAM76A	NM_001143913.2		c.19T>C	p.Cys7Arg	missense	Exon 1 of 9	NP_001137385.1	Q8TAV0-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM76A	ENST00000373954.11	TSL:1 MANE Select	c.19T>C	p.Cys7Arg	missense	Exon 1 of 9	ENSP00000363065.5	Q8TAV0-1
FAM76A	ENST00000010299.10	TSL:1	c.19T>C	p.Cys7Arg	missense	Exon 1 of 10	ENSP00000010299.6	Q8TAV0-3
FAM76A	ENST00000234549.11	TSL:1	c.19T>C	p.Cys7Arg	missense	Exon 1 of 9	ENSP00000234549.7	Q8TAV0-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1140206

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

549452

African (AFR)

AF:

0.00

AC:

AN:

24138

American (AMR)

AF:

0.00

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17472

East Asian (EAS)

AF:

0.00

AC:

AN:

26812

South Asian (SAS)

AF:

0.00

AC:

AN:

37182

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24064

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3158

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

946314

Other (OTH)

AF:

0.00

AC:

AN:

45766

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

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

1.0

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.96

MetaRNN

Pathogenic

0.95

MetaSVM

Uncertain

-0.22

MutationAssessor

Uncertain

2.5

PhyloP100

7.4

PrimateAI

Pathogenic

0.91

PROVEAN

Pathogenic

-9.8

REVEL

Pathogenic

0.72

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.92

MutPred

0.71

Gain of MoRF binding (P = 0.0016)

MVP

0.81

MPC

2.3

ClinPred

1.0

GERP RS

5.4

PromoterAI

-0.032

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.98

gMVP

0.83

Mutation Taster

=24/76

disease causing

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over