NM_001190766.2:c.555A>T

Variant names:

• chr6-17130605-A-T
• rs777881930
• NM_001190766.2:c.555A>T

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.555A>T​(p.Glu185Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000529 in 1,511,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: STMND1 NM_001190766.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.00
• 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=0.04680568).

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.555A>T	p.Glu185Asp	missense	Exon 5 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.555A>T	p.Glu185Asp	missense	Exon 5 of 5	ENSP00000455698.1	H3BQB6
	STMND1	ENST00000907738.1		c.549A>T	p.Glu183Asp	missense	Exon 5 of 5	ENSP00000577797.1
	STMND1	ENST00000354384.5	TSL:5	c.531A>T	p.Glu177Asp	missense	Exon 5 of 5	ENSP00000454363.1	H3BMF7

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00000869 AC: 1 AN: 115012 AF XY: 0.0000160

Gnomad AFR exome AF: 0.000164

Gnomad AMR exome AF: 0.00

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: 0.00000368 AC: 5 AN: 1359322 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 668890

African (AFR) AF: 0.000166 AC: 5 AN: 30140

American (AMR) AF: 0.00 AC: 0 AN: 29984

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24016

East Asian (EAS) AF: 0.00 AC: 0 AN: 35478

South Asian (SAS) AF: 0.00 AC: 0 AN: 74636

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33456

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5566

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1069254

Other (OTH) AF: 0.00 AC: 0 AN: 56792

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152194 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74334

African (AFR) AF: 0.0000724 AC: 3 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15278

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.0000646 AC: 1

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	0.15
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.047	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.0
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.9	N
Sift	Benign	0.094	T
Sift4G	Pathogenic	0.0	D
Vest4		0.23
MVP		0.29
GERP RS		2.3
Varity_R		0.066
gMVP		0.042
Mutation Taster		=61/39	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: rs777881930; hg19: chr6-17130836; COSMIC: COSV100588429;