chr6-17129161-A-G

Variant names:

• chr6-17129161-A-G
• rs1301168675
• NM_001190766.2:c.461A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001190766.2(STMND1):​c.461A>G​(p.Lys154Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000723 in 1,383,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. K154T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: STMND1 NM_001190766.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.12
• Publications: 0 publications found

Genes affected

STMND1 (HGNC:44668): (stathmin domain containing 1) Predicted to enable tubulin binding activity. Predicted to be involved in microtubule depolymerization; neuron projection development; and regulation of microtubule polymerization or depolymerization. Predicted to be active in cytoplasm and neuron projection. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30760533).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001190766.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STMND1	NM_001190766.2	MANE Select	c.461A>G	p.Lys154Arg	missense	Exon 4 of 5	NP_001177695.1	H3BQB6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STMND1	ENST00000536551.6	TSL:5 MANE Select	c.461A>G	p.Lys154Arg	missense	Exon 4 of 5	ENSP00000455698.1	H3BQB6
	STMND1	ENST00000907738.1		c.455A>G	p.Lys152Arg	missense	Exon 4 of 5	ENSP00000577797.1
	STMND1	ENST00000354384.5	TSL:5	c.437A>G	p.Lys146Arg	missense	Exon 4 of 5	ENSP00000454363.1	H3BMF7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1383734 Hom.: 0 Cov.: 30 AF XY: 0.00000146 AC XY: 1 AN XY: 682804

African (AFR) AF: 0.00 AC: 0 AN: 31594

American (AMR) AF: 0.00 AC: 0 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25178

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35728

South Asian (SAS) AF: 0.00 AC: 0 AN: 79234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33880

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078830

Other (OTH) AF: 0.00 AC: 0 AN: 57894

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.096	T
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.31	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.1
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.1	N
Sift	Uncertain	0.025	D
Sift4G	Pathogenic	0.0	D
Vest4		0.33
MVP		0.31
GERP RS		5.8
Varity_R		0.14
gMVP		0.025
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

dbSNP: rs1301168675; hg19: chr6-17129392;