Variant 17-2318883-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_021947.3(SRR):c.353T>C(p.Ile118Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SRR
NM_021947.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.06

Variant links:

Genes affected

SRR (HGNC:14398): (serine racemase) Enables several functions, including L-serine ammonia-lyase activity; PDZ domain binding activity; and anion binding activity. Involved in pyruvate biosynthetic process; response to lipopolysaccharide; and serine family amino acid metabolic process. Located in cytoplasm and neuronal cell body. [provided by Alliance of Genome Resources, Apr 2022]

SRR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.898

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRR	NM_021947.3 linkuse as main transcript	c.353T>C	p.Ile118Thr	missense_variant	4/8	ENST00000344595.10	NP_068766.1	Q9GZT4Q3ZK31Q8N3F4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SRR	ENST00000344595.10 linkuse as main transcript	c.353T>C	p.Ile118Thr	missense_variant	4/8	1	NM_021947.3	ENSP00000339435.5	Q9GZT4
SRR	ENST00000576620.5 linkuse as main transcript	c.353T>C	p.Ile118Thr	missense_variant	4/5	4		ENSP00000461125.1	I3L4B4
SRR	ENST00000574987.1 linkuse as main transcript	c.-95T>C		5_prime_UTR_variant	3/6	4		ENSP00000461343.1	I3L4L3
SRR	ENST00000576848.1 linkuse as main transcript	c.-84-4253T>C		intron_variant		4		ENSP00000476682.1	V9GYE8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461732

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2023

The c.353T>C (p.I118T) alteration is located in exon 4 (coding exon 3) of the SRR gene. This alteration results from a T to C substitution at nucleotide position 353, causing the isoleucine (I) at amino acid position 118 to be replaced by a threonine (T). 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

Pathogenic

0.90

BayesDel_addAF

Pathogenic

0.38

BayesDel_noAF

Pathogenic

0.39

CADD

Uncertain

DANN

Benign

0.75

DEOGEN2

Pathogenic

0.96

D;.

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.92

D;D

M_CAP

Uncertain

0.16

MetaRNN

Pathogenic

0.90

D;D

MetaSVM

Uncertain

0.22

MutationAssessor

Benign

0.16

N;.

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-3.5

D;.

REVEL

Pathogenic

0.74

Sift

Benign

0.056

T;.

Sift4G

Benign

0.16

T;T

Polyphen

0.13

B;.

Vest4

0.86

MutPred

0.81

Gain of glycosylation at I118 (P = 0.0532);Gain of glycosylation at I118 (P = 0.0532);

MVP

0.84

MPC

0.48

ClinPred

0.48

GERP RS

5.2

Varity_R

0.64

gMVP

0.49

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over