rs780141210

chr15-100574025-A-Gchr15-100574025-A-T

Variant summary

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

The NM_001040616.3(LINS1):c.848T>C(p.Met283Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,690 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M283K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: LINS1 NM_001040616.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.89

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=0.10005757).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINS1	NM_001040616.3	c.848T>C	p.Met283Thr	missense_variant	5/7	ENST00000314742.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINS1	ENST00000314742.13	c.848T>C	p.Met283Thr	missense_variant	5/7	5	NM_001040616.3	P1
LINS1	ENST00000561308.5	c.848T>C	p.Met283Thr	missense_variant	5/5	1
LINS1	ENST00000560133.5	c.491T>C	p.Met164Thr	missense_variant	5/5	2
LINS1	ENST00000559149.5	n.1005T>C		non_coding_transcript_exon_variant	5/6	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251154 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135790

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461690 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 727114

Gnomad4 AFR exome AF: 0.0000299

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
Cadd	Benign	19
Dann	Benign	0.82
DEOGEN2	Benign	0.0040	T;.;T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.48	T;T;T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.95	N;N;N
REVEL	Benign	0.036
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.25	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.18
MutPred		0.38		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);.;
MVP		0.088
MPC		0.022
ClinPred		0.058	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.076
gMVP		0.18

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: rs780141210; hg19: chr15-101114230;