10-14966497-C-T

Variant names:

• chr10-14966497-C-T
• rs1843085546
• NM_001080836.3:c.29C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080836.3(MEIG1):​c.29C>T​(p.Ser10Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MEIG1 NM_001080836.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.79

Genes affected

MEIG1 (HGNC:23429): (meiosis/spermiogenesis associated 1) Predicted to act upstream of or within cellular protein localization; manchette assembly; and sperm axoneme assembly. Predicted to be located in cytosol and manchette. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.24844167).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEIG1	NM_001080836.3	c.29C>T	p.Ser10Leu	missense_variant	Exon 2 of 3	ENST00000407572.6	NP_001074305.1
MEIG1	XM_024448136.1	c.122C>T	p.Ser41Leu	missense_variant	Exon 2 of 3		XP_024303904.1
MEIG1	XM_047425662.1	c.29C>T	p.Ser10Leu	missense_variant	Exon 2 of 3		XP_047281618.1
MEIG1	NR_147060.2	n.170+6940C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEIG1	ENST00000407572.6	c.29C>T	p.Ser10Leu	missense_variant	Exon 2 of 3	2	NM_001080836.3	ENSP00000384334.1
MEIG1	ENST00000378240.1	c.29C>T	p.Ser10Leu	missense_variant	Exon 1 of 2	2		ENSP00000367486.1
MEIG1	ENST00000477770.5	n.120-6016C>T		intron_variant	Intron 1 of 1	2
MEIG1	ENST00000496225.2	n.49-3751C>T		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 21, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.29C>T (p.S10L) alteration is located in exon 2 (coding exon 1) of the MEIG1 gene. This alteration results from a C to T substitution at nucleotide position 29, causing the serine (S) at amino acid position 10 to be replaced by a leucine (L). 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	0.13
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.55	D;D
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.88	D;.
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.86	T
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-4.2	D;D
REVEL	Benign	0.12
Sift	Benign	0.030	D;D
Sift4G	Uncertain	0.045	D;D
Polyphen		0.88	P;P
Vest4		0.45
MutPred		0.21		Loss of phosphorylation at S10 (P = 0.015);Loss of phosphorylation at S10 (P = 0.015);
MVP		0.34
MPC		0.053
ClinPred		0.95	D
GERP RS		5.7
Varity_R		0.41
gMVP		0.55

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: rs1843085546; hg19: chr10-15008496;