rs6757698

Variant names:

• chr2-190498770-T-C
• rs6757698
• NM_017694.4:c.2172+1051T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017694.4(MFSD6):​c.2172+1051T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,148 control chromosomes in the GnomAD database, including 5,052 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 0.23 (5052 hom., cov: 32)
• Consequence: MFSD6 NM_017694.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400
• Publications: 5 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFSD6	NM_017694.4	c.2172+1051T>C		intron_variant	Intron 7 of 7	ENST00000392328.6	NP_060164.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFSD6	ENST00000392328.6	c.2172+1051T>C		intron_variant	Intron 7 of 7	2	NM_017694.4	ENSP00000376141.1
MFSD6	ENST00000281416.11	c.2172+1051T>C		intron_variant	Intron 5 of 5	1		ENSP00000281416.7
MFSD6	ENST00000434582.5	c.777+1051T>C		intron_variant	Intron 5 of 6	5		ENSP00000397276.1
MFSD6	ENST00000412482.1	n.69+1051T>C		intron_variant	Intron 1 of 3	3		ENSP00000404511.1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35306 AN: 152030 Hom.: 5050 Cov.: 32

Gnomad AFR AF: 0.0869

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.0774

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.232 AC: 35296 AN: 152148 Hom.: 5052 Cov.: 32 AF XY: 0.231 AC XY: 17191 AN XY: 74372

African (AFR) AF: 0.0867 AC: 3602 AN: 41546

American (AMR) AF: 0.175 AC: 2676 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 613 AN: 3468

East Asian (EAS) AF: 0.0770 AC: 399 AN: 5182

South Asian (SAS) AF: 0.336 AC: 1621 AN: 4820

European-Finnish (FIN) AF: 0.346 AC: 3658 AN: 10562

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21975 AN: 67964

Other (OTH) AF: 0.231 AC: 488 AN: 2112

Alfa AF: 0.282 Hom.: 1411

Bravo AF: 0.207

Asia WGS AF: 0.255 AC: 884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.83
PhyloP100		-0.040
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: rs6757698; hg19: chr2-191363496;