7-101032257-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001040105.2(MUC17):c.841C>A(p.Pro281Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00516 in 1,613,782 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0037 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0053 (31 hom.)
• Consequence: MUC17 NM_001040105.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.45

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0056450367).
• BP6: Variant 7-101032257-C-A is Benign according to our data. Variant chr7-101032257-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2657834.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC17	NM_001040105.2	c.841C>A	p.Pro281Thr	missense_variant	3/13	ENST00000306151.9
MUC17	NR_133665.2	n.896C>A		non_coding_transcript_exon_variant	3/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC17	ENST00000306151.9	c.841C>A	p.Pro281Thr	missense_variant	3/13	1	NM_001040105.2	P1
MUC17	ENST00000379439.3	c.841C>A	p.Pro281Thr	missense_variant, NMD_transcript_variant	3/12	1

Frequencies

GnomAD3 genomes AF: 0.00369 AC: 562 AN: 152150 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00170

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00688

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00372 AC: 935 AN: 251060 Hom.: 3 AF XY: 0.00379 AC XY: 514 AN XY: 135684

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.00142

Gnomad ASJ exome AF: 0.000897

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000557

Gnomad FIN exome AF: 0.00255

Gnomad NFE exome AF: 0.00682

Gnomad OTH exome AF: 0.00392

GnomAD4 exome AF: 0.00531 AC: 7758 AN: 1461514 Hom.: 31 Cov.: 34 AF XY: 0.00510 AC XY: 3708 AN XY: 727032

Gnomad4 AFR exome AF: 0.000597

Gnomad4 AMR exome AF: 0.00141

Gnomad4 ASJ exome AF: 0.000996

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000812

Gnomad4 FIN exome AF: 0.00279

Gnomad4 NFE exome AF: 0.00648

Gnomad4 OTH exome AF: 0.00344

GnomAD4 genome AF: 0.00369 AC: 562 AN: 152268 Hom.: 1 Cov.: 33 AF XY: 0.00334 AC XY: 249 AN XY: 74450

Gnomad4 AFR AF: 0.000554

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.00170

Gnomad4 NFE AF: 0.00688

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00561 Hom.: 4

Bravo AF: 0.00323

TwinsUK AF: 0.00755 AC: 28

ALSPAC AF: 0.00545 AC: 21

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00721 AC: 62

ExAC AF: 0.00399 AC: 484

EpiCase AF: 0.00611

EpiControl AF: 0.00622

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2023

MUC17: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.69
Cadd	Benign	0.38
Dann	Benign	0.31
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0037	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.00084	T
MetaRNN	Benign	0.0056	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.3	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.055
Sift	Pathogenic	0.0	D
Polyphen		0.95	P
Vest4		0.091
MVP		0.040
ClinPred		0.018	T
GERP RS		0.36
Varity_R		0.070
gMVP		0.0066

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: rs150719489; hg19: chr7-100675538; COSMIC: COSV60302219;