rs3811608

Positions:

• chr2-190470331-T-C

Variant summary

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

The NM_017694.4(MFSD6):​c.1630+476T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,234 control chromosomes in the GnomAD database, including 1,849 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (1849 hom., cov: 32)
• Consequence: MFSD6 NM_017694.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.620

Genes affected

MFSD6 (HGNC:24711): (major facilitator superfamily domain containing 6) Predicted to enable MHC class I protein binding activity and MHC class I receptor activity. Predicted to be involved in antigen processing and presentation of exogenous peptide antigen via MHC class I. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

NEMP2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFSD6	NM_017694.4	c.1630+476T>C		intron_variant		ENST00000392328.6	NP_060164.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFSD6	ENST00000392328.6	c.1630+476T>C		intron_variant		2	NM_017694.4	ENSP00000376141	P1
MFSD6	ENST00000281416.11	c.1630+476T>C		intron_variant		1		ENSP00000281416	P1
MFSD6	ENST00000434582.5	c.236+476T>C		intron_variant		5		ENSP00000397276
MFSD6	ENST00000444317.1	c.16+476T>C		intron_variant		4		ENSP00000406837

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22297 AN: 152116 Hom.: 1848 Cov.: 32

Gnomad AFR AF: 0.0758

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.163

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.146 AC: 22299 AN: 152234 Hom.: 1849 Cov.: 32 AF XY: 0.144 AC XY: 10692 AN XY: 74412

Gnomad4 AFR AF: 0.0758

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.161

Alfa AF: 0.160 Hom.: 283

Bravo AF: 0.144

Asia WGS AF: 0.122 AC: 424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.59

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: rs3811608; hg19: chr2-191335057;