6-4068932-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173563.3(FAM217A):​c.1291G>A​(p.Val431Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 1,613,818 control chromosomes in the GnomAD database, including 409,954 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.58 (29851 hom., cov: 32)
  • Exomes 𝑓: 0.72 (380103 hom.)
• 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1704569E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM217A	NM_173563.3	c.1291G>A	p.Val431Ile	missense_variant	Exon 7 of 7	ENST00000274673.8	NP_775834.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM217A	ENST00000274673.8	c.1291G>A	p.Val431Ile	missense_variant	Exon 7 of 7	1	NM_173563.3	ENSP00000274673.3
FAM217A	ENST00000639338.1	c.1693G>A	p.Val565Ile	missense_variant	Exon 9 of 9	5		ENSP00000492773.1
FAM217A	ENST00000380188.2	n.1700G>A		non_coding_transcript_exon_variant	Exon 5 of 5	2
FAM217A	ENST00000469157.5	n.391+4343G>A		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88311 AN: 151934 Hom.: 29858 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.796

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.642

GnomAD3 exomes AF: 0.686 AC: 172443 AN: 251326 Hom.: 61678 AF XY: 0.700 AC XY: 95097 AN XY: 135832

Gnomad AFR exome AF: 0.195

Gnomad AMR exome AF: 0.632

Gnomad ASJ exome AF: 0.793

Gnomad EAS exome AF: 0.629

Gnomad SAS exome AF: 0.742

Gnomad FIN exome AF: 0.732

Gnomad NFE exome AF: 0.747

Gnomad OTH exome AF: 0.726

GnomAD4 exome AF: 0.716 AC: 1046006 AN: 1461766 Hom.: 380103 Cov.: 64 AF XY: 0.718 AC XY: 522471 AN XY: 727172

Gnomad4 AFR exome AF: 0.188

Gnomad4 AMR exome AF: 0.633

Gnomad4 ASJ exome AF: 0.793

Gnomad4 EAS exome AF: 0.630

Gnomad4 SAS exome AF: 0.737

Gnomad4 FIN exome AF: 0.735

Gnomad4 NFE exome AF: 0.734

Gnomad4 OTH exome AF: 0.704

GnomAD4 genome AF: 0.581 AC: 88312 AN: 152052 Hom.: 29851 Cov.: 32 AF XY: 0.584 AC XY: 43371 AN XY: 74324

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.633

Gnomad4 ASJ AF: 0.793

Gnomad4 EAS AF: 0.639

Gnomad4 SAS AF: 0.727

Gnomad4 FIN AF: 0.721

Gnomad4 NFE AF: 0.743

Gnomad4 OTH AF: 0.642

Alfa AF: 0.714 Hom.: 94150

Bravo AF: 0.556

TwinsUK AF: 0.724 AC: 2684

ALSPAC AF: 0.718 AC: 2766

ESP6500AA AF: 0.219 AC: 964

ESP6500EA AF: 0.738 AC: 6347

ExAC AF: 0.679 AC: 82439

Asia WGS AF: 0.673 AC: 2343 AN: 3478

EpiCase AF: 0.751

EpiControl AF: 0.752

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	6.6
DANN	Benign	0.86
DEOGEN2	Benign	0.0085	T;.
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.50	T;T
MetaRNN	Benign	0.0000012	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.5	L;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.44	N;.
REVEL	Benign	0.0050
Sift	Benign	0.22	T;.
Sift4G	Benign	0.22	T;.
Polyphen		0.32	B;.
Vest4		0.015
MPC		0.042
ClinPred		0.0027	T
GERP RS		0.75
Varity_R		0.045
gMVP		0.029

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; COSMIC: COSV51162179; COSMIC: COSV51162179;