1-210241787-A-C

Variant names:

• chr1-210241787-A-C
• NM_019605.5:c.521A>C

Variant summary

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

The NM_019605.5(SERTAD4):​c.521A>C​(p.Lys174Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SERTAD4 NM_019605.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.35

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERTAD4	NM_019605.5	c.521A>C	p.Lys174Thr	missense_variant	Exon 4 of 4	ENST00000367012.4	NP_062551.1
SERTAD4	NM_001375428.1	c.521A>C	p.Lys174Thr	missense_variant	Exon 4 of 4		NP_001362357.1
SERTAD4	NM_001354173.2	c.291+2179A>C		intron_variant	Intron 3 of 4		NP_001341102.1
SERTAD4	XM_047425536.1	c.291+2179A>C		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.521A>C	p.Lys174Thr	missense_variant	Exon 4 of 4	1	NM_019605.5	ENSP00000355979.3
SERTAD4	ENST00000490620.5	n.725A>C		non_coding_transcript_exon_variant	Exon 4 of 4	4
SERTAD4	ENST00000482421.1	n.309+2179A>C		intron_variant	Intron 2 of 3	3
SERTAD4	ENST00000483884.1	n.158+3652A>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 07, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.521A>C (p.K174T) alteration is located in exon 4 (coding exon 3) of the SERTAD4 gene. This alteration results from a A to C substitution at nucleotide position 521, causing the lysine (K) at amino acid position 174 to be replaced by a threonine (T). 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	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	1.1	L
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.075	T
Polyphen		1.0	D
Vest4		0.79
MutPred		0.52		Loss of methylation at K174 (P = 0.0089);
MVP		0.13
MPC		0.51
ClinPred		0.96	D
GERP RS		5.5
Varity_R		0.58
gMVP		0.67

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: chr1-210415132;