rs595413

Positions:

• chr6-4068932-C-A
• chr6-4068932-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173563.3(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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V431I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM217A NM_173563.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.279

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM217A	NM_173563.3	c.1291G>T	p.Val431Phe	missense_variant	7/7	ENST00000274673.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM217A	ENST00000274673.8	c.1291G>T	p.Val431Phe	missense_variant	7/7	1	NM_173563.3	P2
FAM217A	ENST00000639338.1	c.1693G>T	p.Val565Phe	missense_variant	9/9	5		A2
FAM217A	ENST00000380188.2	n.1700G>T		non_coding_transcript_exon_variant	5/5	2
FAM217A	ENST00000469157.5	n.391+4343G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 64

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;.
MutationTaster	Benign	1.0	P
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

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

LitVar

Other links and lift over

dbSNP: rs595413; hg19: chr6-4069166;