rs1128723

Variant names:

• chr2-190501981-A-G
• rs1128723
• NM_017694.4:c.*1763A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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=-0.59).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

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.*1763A>G		3_prime_UTR	Exon 8 of 8	NP_060164.3
	MFSD6	NM_001375986.1		c.*1763A>G		3_prime_UTR	Exon 8 of 8	NP_001362915.1	Q6ZSS7
	MFSD6	NM_001375987.1		c.*1763A>G		3_prime_UTR	Exon 7 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.*1763A>G		3_prime_UTR	Exon 8 of 8	ENSP00000376141.1	Q6ZSS7
	MFSD6	ENST00000281416.11	TSL:1	c.*1763A>G		3_prime_UTR	Exon 6 of 6	ENSP00000281416.7	Q6ZSS7
	MFSD6	ENST00000861426.1		c.*1763A>G		3_prime_UTR	Exon 7 of 7	ENSP00000531485.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0845 AC: 36 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 6

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

African (AFR) AF: 0.185 AC: 7692 AN: 41526

American (AMR) AF: 0.133 AC: 2035 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 412 AN: 3470

East Asian (EAS) AF: 0.305 AC: 1575 AN: 5166

South Asian (SAS) AF: 0.191 AC: 918 AN: 4816

European-Finnish (FIN) AF: 0.0859 AC: 910 AN: 10596

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11914 AN: 67996

Other (OTH) AF: 0.169 AC: 358 AN: 2114

Alfa AF: 0.177 Hom.: 5808

Bravo AF: 0.176

Asia WGS AF: 0.242 AC: 841 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	6.9
DANN	Benign	0.73
PhyloP100		-0.054
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1128723; hg19: chr2-191366707;