chr15-100569422-A-C

Variant names:

• chr15-100569422-A-C
• NM_001040616.3:c.2090T>G

Variant summary

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

The NM_001040616.3(LINS1):​c.2090T>G​(p.Val697Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LINS1 NM_001040616.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.32

Genes affected

LINS1 (HGNC:30922): (lines homolog 1) The Drosophila segment polarity gene lin encodes a protein, lines, which plays important roles in development of the epidermis and hindgut. This gene encodes a protein containing a lines-like domain. This gene is located on chromosome 15 and clustered with the gene encoding ankyrin repeat and SOCS box-containing protein 7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2017]

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=0.094267845).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINS1	NM_001040616.3	c.2090T>G	p.Val697Gly	missense_variant	Exon 7 of 7	ENST00000314742.13	NP_001035706.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINS1	ENST00000314742.13	c.2090T>G	p.Val697Gly	missense_variant	Exon 7 of 7	5	NM_001040616.3	ENSP00000318423.8
LINS1	ENST00000559169.1	n.2365T>G		non_coding_transcript_exon_variant	Exon 2 of 2	2
LINS1	ENST00000560783.1	n.191-4157T>G		intron_variant	Intron 1 of 3	5		ENSP00000474128.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461862 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727238

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual disability, autosomal recessive 27 Uncertain:1

Nov 02, 2021

Revvity Omics, Revvity

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.50
DANN	Benign	0.91
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.017
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.027	D
Polyphen		0.010	B
Vest4		0.064
MutPred		0.59		Gain of relative solvent accessibility (P = 0.0023);
MVP		0.048
MPC		0.023
ClinPred		0.075	T
GERP RS		-5.6
Varity_R		0.081
gMVP		0.13

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: chr15-101109627;