NM_001040105.2:c.8950G>C

Variant names:

• chr7-101040366-G-C
• rs193920784
• NM_001040105.2:c.8950G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040105.2(MUC17):​c.8950G>C​(p.Glu2984Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E2984K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MUC17 NM_001040105.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170
• Publications: 6 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14123705).

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.8950G>C	p.Glu2984Gln	missense	Exon 3 of 13	NP_001035194.1	Q685J3-1
	MUC17	NR_133665.2		n.9005G>C		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.8950G>C	p.Glu2984Gln	missense	Exon 3 of 13	ENSP00000302716.4	Q685J3-1
	MUC17	ENST00000379439.3	TSL:1	n.8950G>C		non_coding_transcript_exon	Exon 3 of 12	ENSP00000368751.3	E7EPM4
	MUC12-AS1	ENST00000844128.1		n.344+23619C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.3
DANN	Benign	0.92
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0022	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.00074	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.017
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.027
Sift	Benign	0.039	D
Polyphen		0.98	D
Vest4		0.043
MutPred		0.13		Gain of MoRF binding (P = 0.0499)
MVP		0.014
ClinPred		0.26	T
GERP RS		-0.98
Varity_R		0.062
gMVP		0.0023
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: rs193920784; hg19: chr7-100683647;