rs751488304

Variant names:

• chr7-101031631-C-A
• rs751488304
• NM_001040105.2:c.215C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-101031631-C-A
• chr7-101031631-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001040105.2(MUC17):​c.215C>A​(p.Thr72Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,550,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000072 (0 hom.)
• Consequence: MUC17 NM_001040105.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.27
• Publications: 0 publications found

Genes affected

MUC17 (HGNC:16800): (mucin 17, cell surface associated) The protein encoded by this gene is a membrane-bound mucin that provides protection to gut epithelial cells. The encoded protein contains about 60 tandem repeats, with each repeat being around 60 aa. N-glycosylation enables the encoded protein to localize on the cell surface, while the C-terminus interacts with the scaffold protein PDZ domain containing 1 (PDZK1). Two transcript variants, one protein-coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Nov 2015]

MUC12-AS1 (HGNC:40382): (MUC12 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05060786).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040105.2. 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
	MUC17	NM_001040105.2	MANE Select	c.215C>A	p.Thr72Lys	missense	Exon 3 of 13	NP_001035194.1	Q685J3-1
	MUC17	NR_133665.2		n.270C>A		non_coding_transcript_exon	Exon 3 of 12

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC17	ENST00000306151.9	TSL:1 MANE Select	c.215C>A	p.Thr72Lys	missense	Exon 3 of 13	ENSP00000302716.4	Q685J3-1
	MUC17	ENST00000379439.3	TSL:1	n.215C>A		non_coding_transcript_exon	Exon 3 of 12	ENSP00000368751.3	E7EPM4
	MUC12-AS1	ENST00000844128.1		n.345-17192G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000297 AC: 6 AN: 202116 AF XY: 0.00000932

Gnomad AFR exome AF: 0.000319

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000104

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000715 AC: 10 AN: 1397800 Hom.: 0 Cov.: 32 AF XY: 0.00000726 AC XY: 5 AN XY: 688558

African (AFR) AF: 0.000191 AC: 6 AN: 31470

American (AMR) AF: 0.0000571 AC: 2 AN: 35024

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21666

East Asian (EAS) AF: 0.00 AC: 0 AN: 39196

South Asian (SAS) AF: 0.00 AC: 0 AN: 74610

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50956

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5432

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1081844

Other (OTH) AF: 0.0000347 AC: 2 AN: 57602

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152210 Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74354

African (AFR) AF: 0.000217 AC: 9 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.18
DANN	Benign	0.46
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0027	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.00059	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.34	N
PhyloP100		-1.3
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.013
Sift	Pathogenic	0.0	D
Polyphen		0.20	B
Vest4		0.096
MVP		0.030
ClinPred		0.018	T
GERP RS		-0.29
Varity_R		0.064
gMVP		0.022
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: rs751488304; hg19: chr7-100674912;