17-9917341-T-A

Variant summary

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

The NM_201433.2(GAS7):c.1318A>T(p.Thr440Ser) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GAS7 NM_201433.2 missense, splice_region
• Scores: Splicing: ADA: 0.1815
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.79

Genes affected

GAS7 (HGNC:4169): (growth arrest specific 7) Growth arrest-specific 7 is expressed primarily in terminally differentiated brain cells and predominantly in mature cerebellar Purkinje neurons. GAS7 plays a putative role in neuronal development. Several transcript variants encoding proteins which vary in the N-terminus have been described. [provided by RefSeq, Jul 2008]

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=0.26341128).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAS7	NM_201433.2	c.1318A>T	p.Thr440Ser	missense_variant, splice_region_variant	14/14	ENST00000432992.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAS7	ENST00000432992.7	c.1318A>T	p.Thr440Ser	missense_variant, splice_region_variant	14/14	1	NM_201433.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Aug 17, 2022

The c.1318A>T (p.T440S) alteration is located in exon 14 (coding exon 14) of the GAS7 gene. This alteration results from a A to T substitution at nucleotide position 1318, causing the threonine (T) at amino acid position 440 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	0.32
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
Cadd	Uncertain	25
Dann	Benign	0.97
Eigen	Benign	-0.16
Eigen_PC	Benign	0.053
FATHMM_MKL	Pathogenic	1.0	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.26	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.80	T
REVEL	Benign	0.18
Sift4G	Uncertain	0.051	T;T;T;T;D;T;D;T
Polyphen		0.061, 0.012	.;.;B;.;B;.;.;.
Vest4		0.49
MutPred		0.38		.;.;Gain of disorder (P = 0.0534);.;.;.;.;.;
MVP		0.37
MPC		0.91
ClinPred		0.81	D
GERP RS		5.0
Varity_R		0.094
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.18
dbscSNV1_RF	Benign	0.44
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: chr17-9820658;