17-2323821-C-G

Variant names:

• chr17-2323821-C-G
• NM_021947.3:c.971C>G

Variant summary

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

The NM_021947.3(SRR):​c.971C>G​(p.Thr324Ser) 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. 13/21 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: SRR NM_021947.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.574

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]

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=0.1633566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRR	NM_021947.3	c.971C>G	p.Thr324Ser	missense_variant	Exon 8 of 8	ENST00000344595.10	NP_068766.1
TSR1	NM_018128.5	c.*375G>C		3_prime_UTR_variant	Exon 15 of 15	ENST00000301364.10	NP_060598.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRR	ENST00000344595.10	c.971C>G	p.Thr324Ser	missense_variant	Exon 8 of 8	1	NM_021947.3	ENSP00000339435.5
TSR1	ENST00000301364	c.*375G>C		3_prime_UTR_variant	Exon 15 of 15	1	NM_018128.5	ENSP00000301364.4
SRR	ENST00000576848.1	c.293C>G	p.Thr98Ser	missense_variant	Exon 3 of 3	4		ENSP00000476682.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 23, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.971C>G (p.T324S) alteration is located in exon 8 (coding exon 7) of the SRR gene. This alteration results from a C to G substitution at nucleotide position 971, causing the threonine (T) at amino acid position 324 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	0.081
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	8.2
DANN	Benign	0.77
DEOGEN2	Benign	0.31	T;T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.37	T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Uncertain	0.54	D
MutationAssessor	Benign	-0.51	N;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.29	N;.
REVEL	Uncertain	0.42
Sift	Benign	0.68	T;.
Sift4G	Benign	0.47	T;T
Polyphen		0.0	B;.
Vest4		0.11
MutPred		0.35		Gain of disorder (P = 0.0469);.;
MVP		0.86
MPC		0.28
ClinPred		0.064	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.064

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: chr17-2227115;