NM_017694.4:c.198C>T

Variant names:

• chr2-190436227-C-T
• rs150345541
• NM_017694.4:c.198C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_017694.4(MFSD6):​c.198C>T​(p.Asn66Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,614,020 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0033 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00088 (12 hom.)
• Consequence: MFSD6 NM_017694.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.02
• Publications: 3 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 2-190436227-C-T is Benign according to our data. Variant chr2-190436227-C-T is described in ClinVar as Benign. ClinVar VariationId is 772854.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.02 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 12 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.198C>T	p.Asn66Asn	synonymous	Exon 3 of 8	NP_060164.3
	MFSD6	NM_001375986.1		c.198C>T	p.Asn66Asn	synonymous	Exon 3 of 8	NP_001362915.1	Q6ZSS7
	MFSD6	NM_001375987.1		c.198C>T	p.Asn66Asn	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.198C>T	p.Asn66Asn	synonymous	Exon 3 of 8	ENSP00000376141.1	Q6ZSS7
	MFSD6	ENST00000281416.11	TSL:1	c.198C>T	p.Asn66Asn	synonymous	Exon 1 of 6	ENSP00000281416.7	Q6ZSS7
	MFSD6	ENST00000861426.1		c.198C>T	p.Asn66Asn	synonymous	Exon 2 of 7	ENSP00000531485.1

Frequencies

GnomAD3 genomes AF: 0.00328 AC: 499 AN: 152200 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00968

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00139 AC: 350 AN: 251098 AF XY: 0.00118

Gnomad AFR exome AF: 0.0101

Gnomad AMR exome AF: 0.00125

Gnomad ASJ exome AF: 0.00615

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000396

Gnomad OTH exome AF: 0.00229

GnomAD4 exome AF: 0.000877 AC: 1282 AN: 1461702 Hom.: 12 Cov.: 30 AF XY: 0.000890 AC XY: 647 AN XY: 727182

African (AFR) AF: 0.0127 AC: 425 AN: 33444

American (AMR) AF: 0.00116 AC: 52 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00670 AC: 175 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.000707 AC: 61 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.0109 AC: 63 AN: 5768

European-Non Finnish (NFE) AF: 0.000344 AC: 382 AN: 1111918

Other (OTH) AF: 0.00204 AC: 123 AN: 60382

GnomAD4 genome AF: 0.00328 AC: 499 AN: 152318 Hom.: 1 Cov.: 33 AF XY: 0.00310 AC XY: 231 AN XY: 74482

African (AFR) AF: 0.00972 AC: 404 AN: 41568

American (AMR) AF: 0.00131 AC: 20 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00692 AC: 24 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10612

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000529 AC: 36 AN: 68034

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.00235 Hom.: 0

Bravo AF: 0.00377

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000948

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	-0.48
CADD	Benign	1.5
DANN	Benign	0.58
PhyloP100		-1.0
PromoterAI		-0.0010	Neutral
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: rs150345541; hg19: chr2-191300953; COSMIC: COSV55622649; COSMIC: COSV55622649;