chr1-27749148-G-A

Variant names:

• chr1-27749148-G-A
• rs184691197
• NM_152660.3:c.593G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152660.3(FAM76A):​c.593G>A​(p.Gly198Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000939 in 1,598,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000090 (0 hom.)
• Consequence: FAM76A NM_152660.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.06
• Publications: 1 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38113996).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM76A	NM_152660.3	MANE Select	c.593G>A	p.Gly198Glu	missense	Exon 6 of 9	NP_689873.1	Q8TAV0-1
	FAM76A	NM_001143912.2		c.695G>A	p.Gly232Glu	missense	Exon 7 of 10	NP_001137384.1	Q8TAV0-3
	FAM76A	NM_001143913.2		c.614+4337G>A		intron	N/A	NP_001137385.1	Q8TAV0-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM76A	ENST00000373954.11	TSL:1 MANE Select	c.593G>A	p.Gly198Glu	missense	Exon 6 of 9	ENSP00000363065.5	Q8TAV0-1
	FAM76A	ENST00000010299.10	TSL:1	c.695G>A	p.Gly232Glu	missense	Exon 7 of 10	ENSP00000010299.6	Q8TAV0-3
	FAM76A	ENST00000530324.5	TSL:1	c.593G>A	p.Gly198Glu	missense	Exon 6 of 8	ENSP00000436176.1	E9PQL1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152160 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000842 AC: 2 AN: 237416 AF XY: 0.00000776

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000572

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000906

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000899 AC: 13 AN: 1445846 Hom.: 0 Cov.: 29 AF XY: 0.00000695 AC XY: 5 AN XY: 719714

African (AFR) AF: 0.00 AC: 0 AN: 32714

American (AMR) AF: 0.00 AC: 0 AN: 39848

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25680

East Asian (EAS) AF: 0.00 AC: 0 AN: 39294

South Asian (SAS) AF: 0.00 AC: 0 AN: 83220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1106410

Other (OTH) AF: 0.0000168 AC: 1 AN: 59694

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152278 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74464

African (AFR) AF: 0.00 AC: 0 AN: 41568

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000386 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.061	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.6	L
PhyloP100		8.1
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.35
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.018	D
Polyphen		1.0	D
Vest4		0.60
MVP		0.90
MPC		1.9
ClinPred		0.87	D
GERP RS		5.5
Varity_R		0.41
gMVP		0.79
Mutation Taster		=46/54	disease causing

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

Other links and lift over

dbSNP: rs184691197; hg19: chr1-28075659;