rs755462199

Variant names:

• chr10-116927879-T-A
• rs755462199
• NM_001127211.3:c.1025A>T

Your query was ambiguous. Multiple possible variants found:

• chr10-116927879-T-A
• chr10-116927879-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS2

The NM_001127211.3(SHTN1):​c.1025A>T​(p.Gln342Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,460,302 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Q342R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SHTN1 NM_001127211.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.93

Genes affected

SHTN1 (HGNC:29319): (shootin 1) Enables identical protein binding activity. Involved in positive regulation of neuron migration. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHTN1	NM_001127211.3	c.1025A>T	p.Gln342Leu	missense_variant	Exon 11 of 17	ENST00000355371.9	NP_001120683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHTN1	ENST00000355371.9	c.1025A>T	p.Gln342Leu	missense_variant	Exon 11 of 17	2	NM_001127211.3	ENSP00000347532.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1460302 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726496

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: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.048	.;.;T;.;.
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;D;D;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.47	T;T;T;T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.4	M;.;M;M;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-3.9	.;D;N;N;D
REVEL	Benign	0.12
Sift	Uncertain	0.013	.;D;D;D;D
Sift4G	Benign	0.16	T;T;T;T;T
Polyphen		0.91	P;.;D;.;.
Vest4		0.60
MutPred		0.17		Loss of ubiquitination at K343 (P = 0.0952);.;Loss of ubiquitination at K343 (P = 0.0952);Loss of ubiquitination at K343 (P = 0.0952);.;
MVP		0.11
MPC		1.2
ClinPred		0.95	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.48

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: rs755462199; hg19: chr10-118687390;