Genetic Variant NM_021947.3:c.1010C>A (chr17-2323860-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021947.3(SRR):c.1010C>A(p.Ser337Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S337F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SRR
NM_021947.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.727

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:

TSR1 (HGNC:25542): (TSR1 ribosome maturation factor) Enables RNA binding activity. Predicted to be involved in endonucleolytic cleavage of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) and maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Predicted to be located in nucleolus. Predicted to be part of preribosome, small subunit precursor. [provided by Alliance of Genome Resources, Apr 2022]

TSR1 links:

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ACMG classification

Classification made for transcript

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=0.08898789).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRR	NM_021947.3 link	c.1010C>A	p.Ser337Tyr	missense_variant	Exon 8 of 8	ENST00000344595.10	NP_068766.1	Q9GZT4Q3ZK31Q8N3F4
TSR1	NM_018128.5 link	c.*336G>T		3_prime_UTR_variant	Exon 15 of 15	ENST00000301364.10	NP_060598.3	Q2NL82

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SRR	ENST00000344595.10 link	c.1010C>A	p.Ser337Tyr	missense_variant	Exon 8 of 8	1	NM_021947.3	ENSP00000339435.5	Q9GZT4
TSR1	ENST00000301364 link	c.*336G>T		3_prime_UTR_variant	Exon 15 of 15	1	NM_018128.5	ENSP00000301364.4	Q2NL82
SRR	ENST00000576848.1 link	c.332C>A	p.Ser111Tyr	missense_variant	Exon 3 of 3	4		ENSP00000476682.1	V9GYE8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461594

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727092

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Uncertain

0.088

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.34

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.63

T;T

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.089

T;T

MetaSVM

Uncertain

0.72

MutationAssessor

Benign

1.1

L;.

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.080

N;.

REVEL

Uncertain

0.35

Sift

Uncertain

0.0050

D;.

Sift4G

Uncertain

0.031

D;D

Polyphen

0.019

B;.

Vest4

0.27

MutPred

0.25

Loss of loop (P = 0.0512);.;

MVP

0.81

MPC

0.45

ClinPred

0.11

GERP RS

-0.60

Varity_R

0.046

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over