1-27744654-G-A

Variant names:

• chr1-27744654-G-A
• rs1390823717
• NM_152660.3:c.355G>A

Variant summary

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

The NM_152660.3(FAM76A):​c.355G>A​(p.Val119Ile) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM76A NM_152660.3 missense, splice_region
• Scores: Splicing: ADA: 0.9838
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.95
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.355G>A	p.Val119Ile	missense splice_region	Exon 5 of 9	NP_689873.1	Q8TAV0-1
	FAM76A	NM_001143912.2		c.457G>A	p.Val153Ile	missense splice_region	Exon 6 of 10	NP_001137384.1	Q8TAV0-3
	FAM76A	NM_001143913.2		c.457G>A	p.Val153Ile	missense splice_region	Exon 6 of 9	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.355G>A	p.Val119Ile	missense splice_region	Exon 5 of 9	ENSP00000363065.5	Q8TAV0-1
	FAM76A	ENST00000010299.10	TSL:1	c.457G>A	p.Val153Ile	missense splice_region	Exon 6 of 10	ENSP00000010299.6	Q8TAV0-3
	FAM76A	ENST00000234549.11	TSL:1	c.457G>A	p.Val153Ile	missense splice_region	Exon 6 of 9	ENSP00000234549.7	Q8TAV0-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Benign	0.19
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.092	T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.9	L
PhyloP100		7.9
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.16
Sift	Benign	0.094	T
Sift4G	Uncertain	0.014	D
Polyphen		1.0	D
Vest4		0.68
MutPred		0.41		Loss of sheet (P = 0.1158)
MVP		0.84
MPC		1.5
ClinPred		0.96	D
GERP RS		5.0
PromoterAI		-0.036	Neutral
Varity_R		0.14
gMVP		0.25
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.98
dbscSNV1_RF	Benign	0.69
SpliceAI score (max)		0.14		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: rs1390823717; hg19: chr1-28071165;