17-8797664-C-T

Variant names:

• chr17-8797664-C-T
• rs2242373
• NM_152599.4:c.1457G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_152599.4(MFSD6L):​c.1457G>A​(p.Arg486His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,613,094 control chromosomes in the GnomAD database, including 30,481 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.19 (2833 hom., cov: 31)
  • Exomes 𝑓: 0.19 (27648 hom.)
• Consequence: MFSD6L NM_152599.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.38

Genes affected

MFSD6L (HGNC:26656): (major facilitator superfamily domain containing 6 like) Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006946951).
• BP6: Variant 17-8797664-C-T is Benign according to our data. Variant chr17-8797664-C-T is described in ClinVar as [Benign]. Clinvar id is 1277181.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFSD6L	NM_152599.4	c.1457G>A	p.Arg486His	missense_variant	Exon 1 of 1	ENST00000329805.6	NP_689812.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFSD6L	ENST00000329805.6	c.1457G>A	p.Arg486His	missense_variant	Exon 1 of 1	6	NM_152599.4	ENSP00000330051.4

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28648 AN: 151934 Hom.: 2830 Cov.: 31

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.0934

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.167

GnomAD3 exomes AF: 0.179 AC: 44895 AN: 250144 Hom.: 4349 AF XY: 0.186 AC XY: 25224 AN XY: 135294

Gnomad AFR exome AF: 0.221

Gnomad AMR exome AF: 0.0984

Gnomad ASJ exome AF: 0.155

Gnomad EAS exome AF: 0.147

Gnomad SAS exome AF: 0.280

Gnomad FIN exome AF: 0.145

Gnomad NFE exome AF: 0.185

Gnomad OTH exome AF: 0.174

GnomAD4 exome AF: 0.191 AC: 278968 AN: 1461042 Hom.: 27648 Cov.: 33 AF XY: 0.194 AC XY: 140820 AN XY: 726796

Gnomad4 AFR exome AF: 0.218

Gnomad4 AMR exome AF: 0.103

Gnomad4 ASJ exome AF: 0.160

Gnomad4 EAS exome AF: 0.139

Gnomad4 SAS exome AF: 0.277

Gnomad4 FIN exome AF: 0.143

Gnomad4 NFE exome AF: 0.192

Gnomad4 OTH exome AF: 0.192

GnomAD4 genome AF: 0.189 AC: 28663 AN: 152052 Hom.: 2833 Cov.: 31 AF XY: 0.186 AC XY: 13824 AN XY: 74318

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.167

Alfa AF: 0.182 Hom.: 3924

Bravo AF: 0.184

TwinsUK AF: 0.181 AC: 672

ALSPAC AF: 0.199 AC: 768

ESP6500AA AF: 0.209 AC: 919

ESP6500EA AF: 0.189 AC: 1625

ExAC AF: 0.185 AC: 22446

Asia WGS AF: 0.249 AC: 865 AN: 3478

EpiCase AF: 0.188

EpiControl AF: 0.182

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0045	T
Eigen	Benign	0.055
Eigen_PC	Benign	-0.066
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.78	T
MetaRNN	Benign	0.0069	T
MetaSVM	Benign	-1.3	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.25
Sift	Benign	0.034	D
Sift4G	Benign	0.072	T
Polyphen		0.99	D
Vest4		0.042
MPC		0.38
ClinPred		0.015	T
GERP RS		4.9
Varity_R		0.044
gMVP		0.23

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: rs2242373; hg19: chr17-8700982; COSMIC: COSV61688077;