6-4068932-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 32 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173563.3. 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>A	p.Val431Ile	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>A	p.Val431Ile	missense	Exon 7 of 7	ENSP00000274673.3
	FAM217A	ENST00000639338.1	TSL:5	c.1693G>A	p.Val565Ile	missense	Exon 9 of 9	ENSP00000492773.1
	FAM217A	ENST00000380188.2	TSL:2	n.1700G>A		non_coding_transcript_exon	Exon 5 of 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

GnomAD2 exomes AF: 0.686 AC: 172443 AN: 251326 AF XY: 0.700

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 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

African (AFR) AF: 0.188 AC: 6294 AN: 33476

American (AMR) AF: 0.633 AC: 28312 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.793 AC: 20708 AN: 26126

East Asian (EAS) AF: 0.630 AC: 24995 AN: 39688

South Asian (SAS) AF: 0.737 AC: 63601 AN: 86244

European-Finnish (FIN) AF: 0.735 AC: 39258 AN: 53418

Middle Eastern (MID) AF: 0.797 AC: 4595 AN: 5768

European-Non Finnish (NFE) AF: 0.734 AC: 815742 AN: 1111936

Other (OTH) AF: 0.704 AC: 42501 AN: 60392

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

African (AFR) AF: 0.208 AC: 8634 AN: 41444

American (AMR) AF: 0.633 AC: 9676 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.793 AC: 2751 AN: 3468

East Asian (EAS) AF: 0.639 AC: 3300 AN: 5166

South Asian (SAS) AF: 0.727 AC: 3505 AN: 4818

European-Finnish (FIN) AF: 0.721 AC: 7620 AN: 10574

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.743 AC: 50492 AN: 67984

Other (OTH) AF: 0.642 AC: 1358 AN: 2114

Alfa AF: 0.696 Hom.: 167836

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 v4.9

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
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.28
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
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV51162179; COSMIC: COSV51162179;