1-27759595-A-G

Variant names:

• chr1-27759595-A-G
• NM_152660.3:c.805A>G

Variant summary

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

The NM_152660.3(FAM76A):​c.805A>G​(p.Lys269Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: FAM76A NM_152660.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.59
• 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.805A>G	p.Lys269Glu	missense	Exon 8 of 9	NP_689873.1	Q8TAV0-1
	FAM76A	NM_001143912.2		c.907A>G	p.Lys303Glu	missense	Exon 9 of 10	NP_001137384.1	Q8TAV0-3
	FAM76A	NM_001143913.2		c.820A>G	p.Lys274Glu	missense	Exon 8 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.805A>G	p.Lys269Glu	missense	Exon 8 of 9	ENSP00000363065.5	Q8TAV0-1
	FAM76A	ENST00000010299.10	TSL:1	c.907A>G	p.Lys303Glu	missense	Exon 9 of 10	ENSP00000010299.6	Q8TAV0-3
	FAM76A	ENST00000234549.11	TSL:1	c.820A>G	p.Lys274Glu	missense	Exon 8 of 9	ENSP00000234549.7	Q8TAV0-4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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	0.68
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.9	L
PhyloP100		8.6
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.24
Sift	Benign	0.11	T
Sift4G	Uncertain	0.0040	D
Polyphen		0.98	D
Vest4		0.80
MutPred		0.27		Loss of MoRF binding (P = 8e-04)
MVP		0.78
MPC		2.0
ClinPred		0.98	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.41
gMVP		0.41
Mutation Taster		=88/12	polymorphism

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

hg19: chr1-28086106;