6-17115062-T-G

Variant names:

• chr6-17115062-T-G
• rs532291638
• NM_001190766.2:c.182T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001190766.2(STMND1):​c.182T>G​(p.Val61Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000111 in 1,535,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V61A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000087 (0 hom.)
• Consequence: STMND1 NM_001190766.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.119
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06761199).

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.182T>G	p.Val61Gly	missense	Exon 2 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.182T>G	p.Val61Gly	missense	Exon 2 of 5	ENSP00000455698.1	H3BQB6
	STMND1	ENST00000907738.1		c.182T>G	p.Val61Gly	missense	Exon 2 of 5	ENSP00000577797.1
	STMND1	ENST00000354384.5	TSL:5	c.158T>G	p.Val53Gly	missense	Exon 2 of 5	ENSP00000454363.1	H3BMF7

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152142 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000223 AC: 3 AN: 134382 AF XY: 0.0000137

Gnomad AFR exome AF: 0.000156

Gnomad AMR exome AF: 0.0000819

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000867 AC: 12 AN: 1383724 Hom.: 0 Cov.: 30 AF XY: 0.00000879 AC XY: 6 AN XY: 682798

African (AFR) AF: 0.000190 AC: 6 AN: 31582

American (AMR) AF: 0.0000561 AC: 2 AN: 35682

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 35726

South Asian (SAS) AF: 0.00 AC: 0 AN: 79224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33890

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00000371 AC: 4 AN: 1078850

Other (OTH) AF: 0.00 AC: 0 AN: 57898

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152258 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74450

African (AFR) AF: 0.0000963 AC: 4 AN: 41554

American (AMR) AF: 0.0000654 AC: 1 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000529

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	5.0
DANN	Benign	0.79
DEOGEN2	Benign	0.025	T
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.068	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.12
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.92	N
Sift	Benign	0.078	T
Sift4G	Benign	0.090	T
Vest4		0.12
MVP		0.40
GERP RS		0.18
Varity_R		0.059
gMVP		0.14
Mutation Taster		=94/6	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: rs532291638; hg19: chr6-17115293;