NM_021947.3:c.1010C>A

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

6
13

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]
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]

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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
SRRNM_021947.3 linkc.1010C>A p.Ser337Tyr missense_variant Exon 8 of 8 ENST00000344595.10 NP_068766.1 Q9GZT4Q3ZK31Q8N3F4
TSR1NM_018128.5 linkc.*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 Appris UniProt
SRRENST00000344595.10 linkc.1010C>A p.Ser337Tyr missense_variant Exon 8 of 8 1 NM_021947.3 ENSP00000339435.5 Q9GZT4
TSR1ENST00000301364 linkc.*336G>T 3_prime_UTR_variant Exon 15 of 15 1 NM_018128.5 ENSP00000301364.4 Q2NL82
SRRENST00000576848.1 linkc.332C>A p.Ser111Tyr missense_variant Exon 3 of 3 4 ENSP00000476682.1 V9GYE8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461594
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
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.:
32

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
D
BayesDel_noAF
Benign
-0.11
CADD
Benign
17
DANN
Benign
0.91
DEOGEN2
Benign
0.34
T;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.16
N
LIST_S2
Benign
0.63
T;T
M_CAP
Uncertain
0.17
D
MetaRNN
Benign
0.089
T;T
MetaSVM
Uncertain
0.72
D
MutationAssessor
Benign
1.1
L;.
PrimateAI
Benign
0.46
T
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
T
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.

Other links and lift over

hg19: chr17-2227154; API