1-210238031-G-A

Variant names:

• chr1-210238031-G-A
• NM_019605.5:c.71G>A

Variant summary

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

The NM_019605.5(SERTAD4):​c.71G>A​(p.Gly24Glu) 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. 14/20 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)
• Consequence: SERTAD4 NM_019605.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.36

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.111958236).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERTAD4	NM_019605.5	c.71G>A	p.Gly24Glu	missense_variant	Exon 2 of 4	ENST00000367012.4	NP_062551.1
SERTAD4	NM_001375428.1	c.71G>A	p.Gly24Glu	missense_variant	Exon 2 of 4		NP_001362357.1
SERTAD4	NM_001354173.2	c.71G>A	p.Gly24Glu	missense_variant	Exon 2 of 5		NP_001341102.1
SERTAD4	XM_047425536.1	c.71G>A	p.Gly24Glu	missense_variant	Exon 2 of 5		XP_047281492.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERTAD4	ENST00000367012.4	c.71G>A	p.Gly24Glu	missense_variant	Exon 2 of 4	1	NM_019605.5	ENSP00000355979.3
SERTAD4	ENST00000482421.1	n.89G>A		non_coding_transcript_exon_variant	Exon 1 of 4	3
SERTAD4	ENST00000483884.1	n.54G>A		non_coding_transcript_exon_variant	Exon 1 of 3	3
SERTAD4	ENST00000490620.5	n.275G>A		non_coding_transcript_exon_variant	Exon 2 of 4	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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 10, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.71G>A (p.G24E) alteration is located in exon 2 (coding exon 1) of the SERTAD4 gene. This alteration results from a G to A substitution at nucleotide position 71, causing the glycine (G) at amino acid position 24 to be replaced by a glutamic acid (E). 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	0.18
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Benign	0.78
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.041
FATHMM_MKL	Benign	0.61	D
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.16
Sift	Benign	0.42	T
Sift4G	Benign	1.0	T
Polyphen		0.020	B
Vest4		0.30
MutPred		0.41		Gain of solvent accessibility (P = 0.0145);
MVP		0.043
MPC		0.49
ClinPred		0.41	T
GERP RS		4.3
Varity_R		0.10
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-210411376; COSMIC: COSV65400315; COSMIC: COSV65400315;