chr6-4068932-C-A

Variant names:

• chr6-4068932-C-A
• rs595413
• NM_173563.3:c.1291G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000274673.8(FAM217A):​c.1291G>T​(p.Val431Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM217A ENST00000274673.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.279
• Publications: 32 publications found

Genes affected

FAM217A (HGNC:21362): (family with sequence similarity 217 member A)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18551368).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000274673.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM217A	NM_173563.3	MANE Select	c.1291G>T	p.Val431Phe	missense	Exon 7 of 7	NP_775834.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM217A	ENST00000274673.8	TSL:1 MANE Select	c.1291G>T	p.Val431Phe	missense	Exon 7 of 7	ENSP00000274673.3
	FAM217A	ENST00000639338.1	TSL:5	c.1693G>T	p.Val565Phe	missense	Exon 9 of 9	ENSP00000492773.1
	FAM217A	ENST00000380188.2	TSL:2	n.1700G>T		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 64

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 167836

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.055	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.28
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.13
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.99	D
Vest4		0.31
MutPred		0.24		Loss of MoRF binding (P = 0.0876)
MVP		0.16
MPC		0.22
ClinPred		0.73	D
GERP RS		0.75
Varity_R		0.18
gMVP		0.14
Mutation Taster		=95/5	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

dbSNP: rs595413; hg19: chr6-4069166;