chr19-40442024-C-A

Variant names:

• chr19-40442024-C-A
• rs1321943361
• NM_203344.3:c.57G>T

Variant summary

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

The NM_203344.3(SERTAD3):​c.57G>T​(p.Trp19Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000735 in 1,359,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: SERTAD3 NM_203344.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.771

Genes affected

SERTAD3 (HGNC:17931): (SERTA domain containing 3) The protein encoded by this gene was identified in a yeast two-hybrid assay employing the second subunit of human replication protein A as bait. It is localized to the nucleus and its expression is significantly higher in cancer cell lines compared to normal cell lines. This protein has also been shown to be a strong transcriptional co-activator. Alternative splicing has been observed at this locus and two variants, both encoding the same protein, have been identified. [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=0.15133289).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERTAD3	NM_203344.3	c.57G>T	p.Trp19Cys	missense_variant	Exon 2 of 2	ENST00000322354.4	NP_976219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERTAD3	ENST00000322354.4	c.57G>T	p.Trp19Cys	missense_variant	Exon 2 of 2	1	NM_203344.3	ENSP00000325414.2
SERTAD3	ENST00000392028.8	c.57G>T	p.Trp19Cys	missense_variant	Exon 2 of 2	1		ENSP00000375882.3
SERTAD3	ENST00000599706.1	c.57G>T	p.Trp19Cys	missense_variant	Exon 2 of 2	2		ENSP00000469245.1
SERTAD3	ENST00000596456.1	c.57G>T	p.Trp19Cys	missense_variant	Exon 3 of 3	3		ENSP00000472999.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.35e-7 AC: 1 AN: 1359686 Hom.: 0 Cov.: 32 AF XY: 0.00000150 AC XY: 1 AN XY: 666510

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.39e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 30, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.57G>T (p.W19C) alteration is located in exon 2 (coding exon 1) of the SERTAD3 gene. This alteration results from a G to T substitution at nucleotide position 57, causing the tryptophan (W) at amino acid position 19 to be replaced by a cysteine (C). 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	Uncertain	0.38
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.076	T;T;.;.
Eigen	Benign	0.18
Eigen_PC	Benign	0.17
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.49	.;T;T;T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.55	N;N;.;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.3	N;N;.;.
REVEL	Benign	0.18
Sift	Benign	0.22	T;T;.;.
Sift4G	Pathogenic	0.0	D;D;.;.
Polyphen		1.0	D;D;.;.
Vest4		0.28
MutPred		0.20		Gain of loop (P = 0.069);Gain of loop (P = 0.069);Gain of loop (P = 0.069);Gain of loop (P = 0.069);
MVP		0.25
MPC		0.91
ClinPred		0.84	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs1321943361; hg19: chr19-40947931;