Variant chr6-30949260-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_080870.4(MUCL3):c.796A>G(p.Thr266Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,397,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MUCL3
NM_080870.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.68

Variant links:

Genes affected

MUCL3 (HGNC:21666): (mucin like 3) Predicted to be located in cytoplasm and plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MUCL3 links:

SFTA2 (HGNC:18386): (surfactant associated 2) Predicted to be located in Golgi apparatus; extracellular region; and transport vesicle. [provided by Alliance of Genome Resources, Apr 2022]

SFTA2 links:

HCG21 (HGNC:):

HCG21 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.083660364).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUCL3	NM_080870.4 linkuse as main transcript	c.796A>G	p.Thr266Ala	missense_variant	2/3	ENST00000462446.6	NP_543146.2
HCG21	NR_138040.1 linkuse as main transcript	n.257-2682T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MUCL3	ENST00000462446.6 linkuse as main transcript	c.796A>G	p.Thr266Ala	missense_variant	2/3	5	NM_080870.4	ENSP00000417182.1	E9PEI6
MUCL3	ENST00000636043.1 linkuse as main transcript	c.997A>G	p.Thr333Ala	missense_variant	5/6	5		ENSP00000490368.1	A0A1B0GV46
SFTA2	ENST00000634371.1 linkuse as main transcript	c.-9+3102T>C		intron_variant		5		ENSP00000489572.1	A0A0U1RRK6
HCG21	ENST00000419481.1 linkuse as main transcript	n.225-2901T>C		intron_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1397518

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689284

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 04, 2024

The c.796A>G (p.T266A) alteration is located in exon 2 (coding exon 2) of the DPCR1 gene. This alteration results from a A to G substitution at nucleotide position 796, causing the threonine (T) at amino acid position 266 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

T;T;T

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.43

T;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.084

T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.2

.;N;.

REVEL

Benign

0.061

Sift4G

Pathogenic

0.0

.;D;T

Polyphen

0.87

.;P;.

Vest4

0.19, 0.078

MutPred

0.12

.;Gain of MoRF binding (P = 0.0881);Gain of MoRF binding (P = 0.0881);

MVP

0.095

MPC

0.49

ClinPred

0.16

GERP RS

-0.34

Varity_R

0.041

gMVP

0.42

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over