Genetic Variant SERTAD4:p.Asp120Asn (chr1-210241624-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_019605.5(SERTAD4):c.358G>A(p.Asp120Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000137 in 1,610,512 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000067 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

SERTAD4
NM_019605.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.96

Variant links:

Genes affected

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

SERTAD4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 link	c.358G>A	p.Asp120Asn	missense_variant	Exon 4 of 4	ENST00000367012.4	NP_062551.1	Q9NUC0
SERTAD4	NM_001375428.1 link	c.358G>A	p.Asp120Asn	missense_variant	Exon 4 of 4		NP_001362357.1
SERTAD4	NM_001354173.2 link	c.291+2016G>A		intron_variant	Intron 3 of 4		NP_001341102.1
SERTAD4	XM_047425536.1 link	c.291+2016G>A		intron_variant	Intron 3 of 4		XP_047281492.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SERTAD4	ENST00000367012.4 link	c.358G>A	p.Asp120Asn	missense_variant	Exon 4 of 4	1	NM_019605.5	ENSP00000355979.3	Q9NUC0
SERTAD4	ENST00000490620.5 link	n.562G>A		non_coding_transcript_exon_variant	Exon 4 of 4	4
SERTAD4	ENST00000482421.1 link	n.309+2016G>A		intron_variant	Intron 2 of 3	3
SERTAD4	ENST00000483884.1 link	n.158+3489G>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.0000669

AC:

AN:

149484

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000759

AC:

AN:

250370

Hom.:

AF XY:

0.0000887

AC XY:

AN XY:

135358

show subpopulations

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000150

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.000144

AC:

211

AN:

1461028

Hom.:

Cov.:

AF XY:

0.000154

AC XY:

112

AN XY:

726744

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000182

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.0000669

AC:

AN:

149484

Hom.:

Cov.:

AF XY:

0.0000689

AC XY:

AN XY:

72602

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000148

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000987

Hom.:

Bravo

AF:

0.0000982

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.358G>A (p.D120N) alteration is located in exon 4 (coding exon 3) of the SERTAD4 gene. This alteration results from a G to A substitution at nucleotide position 358, causing the aspartic acid (D) at amino acid position 120 to be replaced by an asparagine (N). 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

0.76

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.97

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.57

MetaSVM

Uncertain

-0.25

MutationAssessor

Benign

1.8

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-3.7

REVEL

Uncertain

0.61

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0070

Polyphen

1.0

Vest4

0.59

MVP

0.41

MPC

0.46

ClinPred

0.56

GERP RS

5.7

Varity_R

0.59

gMVP

0.42

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over