2-190501853-T-G

Position:

• chr2-190501853-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_017694.4(MFSD6):​c.*1635T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,546 control chromosomes in the GnomAD database, including 5,068 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 (5046 hom., cov: 32)
  • Exomes 𝑓: 0.32 (22 hom.)
• Consequence: MFSD6 NM_017694.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.55

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFSD6	NM_017694.4	c.*1635T>G		3_prime_UTR_variant	8/8	ENST00000392328.6	NP_060164.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFSD6	ENST00000392328.6	c.*1635T>G		3_prime_UTR_variant	8/8	2	NM_017694.4	ENSP00000376141	P1
MFSD6	ENST00000281416.11	c.*1635T>G		3_prime_UTR_variant	6/6	1		ENSP00000281416	P1
MFSD6	ENST00000434582.5	c.*1828T>G		3_prime_UTR_variant	7/7	5		ENSP00000397276
MFSD6	ENST00000412482.1	c.*58+1577T>G		intron_variant, NMD_transcript_variant		3		ENSP00000404511

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35230 AN: 151996 Hom.: 5045 Cov.: 32

Gnomad AFR AF: 0.0851

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.0790

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.230

GnomAD4 exome AF: 0.319 AC: 138 AN: 432 Hom.: 22 Cov.: 0 AF XY: 0.338 AC XY: 88 AN XY: 260

Gnomad4 FIN exome AF: 0.317

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.232 AC: 35217 AN: 152114 Hom.: 5046 Cov.: 32 AF XY: 0.231 AC XY: 17143 AN XY: 74360

Gnomad4 AFR AF: 0.0849

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.0783

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.229

Alfa AF: 0.286 Hom.: 6551

Bravo AF: 0.206

Asia WGS AF: 0.253 AC: 877 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Benign	0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs7721; hg19: chr2-191366579; COSMIC: COSV55622345; COSMIC: COSV55622345;