3-151436701-A-C

Position:

• chr3-151436701-A-C

Variant summary

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

The NM_178822.5(IGSF10):​c.7860T>G​(p.Ile2620Met) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: IGSF10 NM_178822.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.248

Genes affected

IGSF10 (HGNC:26384): (immunoglobulin superfamily member 10) Predicted to be involved in regulation of neuron migration. Predicted to act upstream of or within ossification. Located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

MED12L (HGNC:16050): (mediator complex subunit 12L) The protein encoded by this gene is part of the Mediator complex, which is involved in transcriptional coactivation of nearly all RNA polymerase II-dependent genes. The Mediator complex links gene-specific transcriptional activators with the basal transcription machinery. [provided by RefSeq, May 2010]

IGSF10 (HGNC:):

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=0.12684625).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF10	NM_178822.5	c.7860T>G	p.Ile2620Met	missense_variant	8/8	ENST00000282466.4	NP_849144.2
MED12L	NM_001393769.1	c.*3897A>C		downstream_gene_variant		ENST00000687756.1	NP_001380698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGSF10	ENST00000282466.4	c.7860T>G	p.Ile2620Met	missense_variant	8/8	1	NM_178822.5	ENSP00000282466.3
MED12L	ENST00000687756.1	c.*3897A>C		downstream_gene_variant			NM_001393769.1	ENSP00000508695.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 13, 2023

The c.7860T>G (p.I2620M) alteration is located in exon 6 (coding exon 6) of the IGSF10 gene. This alteration results from a T to G substitution at nucleotide position 7860, causing the isoleucine (I) at amino acid position 2620 to be replaced by a methionine (M). 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	0.14
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	3.7
DANN	Benign	0.85
DEOGEN2	Benign	0.022	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.29
Sift	Benign	0.042	D
Sift4G	Benign	0.18	T
Polyphen		0.70	P
Vest4		0.23
MutPred		0.57		Gain of disorder (P = 0.0407);
MVP		0.62
MPC		0.043
ClinPred		0.20	T
GERP RS		-3.7
Varity_R		0.12
gMVP		0.53

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.

Other links and lift over

hg19: chr3-151154489;