rs113040578

Variant names:

• chr2-190436914-C-T
• rs113040578
• NM_017694.4:c.885C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_017694.4(MFSD6):​c.885C>T​(p.Val295Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 1,614,172 control chromosomes in the GnomAD database, including 118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0077 (5 hom., cov: 32)
  • Exomes 𝑓: 0.011 (113 hom.)
• Consequence: MFSD6 NM_017694.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.680
• Publications: 2 publications found

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:33700): (nuclear envelope integral membrane protein 2) Predicted to be located in nuclear inner membrane. Predicted to be integral component of membrane. Predicted to be active in nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000309564 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 2-190436914-C-T is Benign according to our data. Variant chr2-190436914-C-T is described in ClinVar as Benign. ClinVar VariationId is 777960.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.68 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017694.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFSD6	NM_017694.4	MANE Select	c.885C>T	p.Val295Val	synonymous	Exon 3 of 8	NP_060164.3
	MFSD6	NM_001375986.1		c.885C>T	p.Val295Val	synonymous	Exon 3 of 8	NP_001362915.1	Q6ZSS7
	MFSD6	NM_001375987.1		c.885C>T	p.Val295Val	synonymous	Exon 2 of 7	NP_001362916.1	Q6ZSS7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFSD6	ENST00000392328.6	TSL:2 MANE Select	c.885C>T	p.Val295Val	synonymous	Exon 3 of 8	ENSP00000376141.1	Q6ZSS7
	MFSD6	ENST00000281416.11	TSL:1	c.885C>T	p.Val295Val	synonymous	Exon 1 of 6	ENSP00000281416.7	Q6ZSS7
	MFSD6	ENST00000861426.1		c.885C>T	p.Val295Val	synonymous	Exon 2 of 7	ENSP00000531485.1

Frequencies

GnomAD3 genomes AF: 0.00775 AC: 1180 AN: 152186 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00188

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00511

Gnomad ASJ AF: 0.0550

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.00509

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0109

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00846 AC: 2127 AN: 251492 AF XY: 0.00852

Gnomad AFR exome AF: 0.00252

Gnomad AMR exome AF: 0.00396

Gnomad ASJ exome AF: 0.0433

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00513

Gnomad NFE exome AF: 0.0110

Gnomad OTH exome AF: 0.00993

GnomAD4 exome AF: 0.0111 AC: 16193 AN: 1461868 Hom.: 113 Cov.: 33 AF XY: 0.0108 AC XY: 7872 AN XY: 727234

African (AFR) AF: 0.00185 AC: 62 AN: 33478

American (AMR) AF: 0.00429 AC: 192 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0425 AC: 1111 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00311 AC: 268 AN: 86244

European-Finnish (FIN) AF: 0.00483 AC: 258 AN: 53420

Middle Eastern (MID) AF: 0.00659 AC: 38 AN: 5768

European-Non Finnish (NFE) AF: 0.0121 AC: 13481 AN: 1112002

Other (OTH) AF: 0.0129 AC: 782 AN: 60396

GnomAD4 genome AF: 0.00774 AC: 1179 AN: 152304 Hom.: 5 Cov.: 32 AF XY: 0.00733 AC XY: 546 AN XY: 74472

African (AFR) AF: 0.00188 AC: 78 AN: 41560

American (AMR) AF: 0.00510 AC: 78 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0550 AC: 191 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4830

European-Finnish (FIN) AF: 0.00509 AC: 54 AN: 10608

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0109 AC: 743 AN: 68030

Other (OTH) AF: 0.00993 AC: 21 AN: 2114

Alfa AF: 0.0121 Hom.: 7

Bravo AF: 0.00789

Asia WGS AF: 0.00173 AC: 7 AN: 3478

EpiCase AF: 0.0125

EpiControl AF: 0.0124

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	5.8
DANN	Benign	0.68
PhyloP100		0.68
Mutation Taster		=100/0	polymorphism

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: rs113040578; hg19: chr2-191301640;