1-210241825-C-G

Variant names:

• chr1-210241825-C-G
• rs770581752
• NM_019605.5:c.559C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_019605.5(SERTAD4):​c.559C>G​(p.His187Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000205 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: SERTAD4 NM_019605.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.74

Genes affected

SERTAD4 (HGNC:25236): (SERTA domain containing 4) Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4040818).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERTAD4	NM_019605.5	c.559C>G	p.His187Asp	missense_variant	Exon 4 of 4	ENST00000367012.4	NP_062551.1
SERTAD4	NM_001375428.1	c.559C>G	p.His187Asp	missense_variant	Exon 4 of 4		NP_001362357.1
SERTAD4	NM_001354173.2	c.291+2217C>G		intron_variant	Intron 3 of 4		NP_001341102.1
SERTAD4	XM_047425536.1	c.291+2217C>G		intron_variant	Intron 3 of 4		XP_047281492.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERTAD4	ENST00000367012.4	c.559C>G	p.His187Asp	missense_variant	Exon 4 of 4	1	NM_019605.5	ENSP00000355979.3
SERTAD4	ENST00000490620.5	n.763C>G		non_coding_transcript_exon_variant	Exon 4 of 4	4
SERTAD4	ENST00000482421.1	n.309+2217C>G		intron_variant	Intron 2 of 3	3
SERTAD4	ENST00000483884.1	n.158+3690C>G		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.0000438 AC: 11 AN: 251374 Hom.: 0 AF XY: 0.0000442 AC XY: 6 AN XY: 135892

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000359

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000205 AC: 30 AN: 1461892 Hom.: 0 Cov.: 35 AF XY: 0.0000316 AC XY: 23 AN XY: 727248

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: 0.000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ExAC AF: 0.0000247 AC: 3

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.559C>G (p.H187D) alteration is located in exon 4 (coding exon 3) of the SERTAD4 gene. This alteration results from a C to G substitution at nucleotide position 559, causing the histidine (H) at amino acid position 187 to be replaced by an aspartic acid (D). 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	0.33
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Pathogenic	0.15
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.1	L
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.19
Sift	Uncertain	0.019	D
Sift4G	Benign	0.076	T
Polyphen		0.95	P
Vest4		0.58
MutPred		0.45		Gain of relative solvent accessibility (P = 0.0483);
MVP		0.42
MPC		0.47
ClinPred		0.20	T
GERP RS		5.5
Varity_R		0.21
gMVP		0.69

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

Other links and lift over

dbSNP: rs770581752; hg19: chr1-210415170;