rs1128723

Positions:

• chr2-190501981-A-G

Variant summary

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

The NM_017694.4(MFSD6):​c.*1763A>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 0.171 in 152,616 control chromosomes in the GnomAD database, including 2,385 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 0.17 (2385 hom., cov: 32)
  • Exomes 𝑓: 0.083 (0 hom.)
• Consequence: MFSD6 NM_017694.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540

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=-0.59).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFSD6	NM_017694.4	c.*1763A>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.*1763A>G		3_prime_UTR_variant	8/8	2	NM_017694.4	ENSP00000376141	P1
MFSD6	ENST00000281416.11	c.*1763A>G		3_prime_UTR_variant	6/6	1		ENSP00000281416	P1
MFSD6	ENST00000434582.5	c.*1956A>G		3_prime_UTR_variant	7/7	5		ENSP00000397276
MFSD6	ENST00000412482.1	c.*58+1705A>G		intron_variant, NMD_transcript_variant		3		ENSP00000404511

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26045 AN: 152068 Hom.: 2383 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.0859

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.165

GnomAD4 exome AF: 0.0829 AC: 36 AN: 434 Hom.: 0 Cov.: 0 AF XY: 0.0802 AC XY: 21 AN XY: 262

Gnomad4 FIN exome AF: 0.0845

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.171 AC: 26063 AN: 152182 Hom.: 2385 Cov.: 32 AF XY: 0.167 AC XY: 12459 AN XY: 74408

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.0859

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.169

Alfa AF: 0.177 Hom.: 4003

Bravo AF: 0.176

Asia WGS AF: 0.242 AC: 841 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	6.9
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1128723; hg19: chr2-191366707;