chr20-13279765-G-T

Position:

• chr20-13279765-G-T

Variant summary

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

The NM_080826.2(ISM1):​c.510G>T​(p.Arg170Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ISM1 NM_080826.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.13

Genes affected

ISM1 (HGNC:16213): (isthmin 1) Predicted to be involved in negative regulation of angiogenesis. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

TASP1 (HGNC:):

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=0.143493).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ISM1	NM_080826.2	c.510G>T	p.Arg170Ser	missense_variant	3/6	ENST00000262487.5	NP_543016.1
ISM1	XM_017027680.2	c.510G>T	p.Arg170Ser	missense_variant	3/7		XP_016883169.1
TASP1	XR_001754319.3	n.1369+36205C>A		intron_variant
TASP1	XR_007067463.1	n.1370-13583C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ISM1	ENST00000262487.5	c.510G>T	p.Arg170Ser	missense_variant	3/6	5	NM_080826.2	ENSP00000262487.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 30, 2024

The c.510G>T (p.R170S) alteration is located in exon 3 (coding exon 3) of the ISM1 gene. This alteration results from a G to T substitution at nucleotide position 510, causing the arginine (R) at amino acid position 170 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.0090	T
Eigen	Benign	-0.052
Eigen_PC	Benign	0.092
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.15
Sift	Benign	0.45	T
Sift4G	Benign	0.70	T
Polyphen		0.65	P
Vest4		0.35
MutPred		0.31		Loss of MoRF binding (P = 0.0322);
MVP		0.13
MPC		0.039
ClinPred		0.47	T
GERP RS		4.9
Varity_R		0.18
gMVP		0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-13260412;