19-40423018-T-C

Variant names:

• chr19-40423018-T-C
• rs2079603707
• NM_013376.4:c.529A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_013376.4(SERTAD1):​c.529A>G​(p.Ile177Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,424,870 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I177F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SERTAD1 NM_013376.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.34
• Publications: 0 publications found

Genes affected

SERTAD1 (HGNC:17932): (SERTA domain containing 1) Predicted to be involved in epigenetic maintenance of chromatin in transcription-competent conformation. Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Predicted to be located in cytoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4169467).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013376.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERTAD1	NM_013376.4	MANE Select	c.529A>G	p.Ile177Val	missense	Exon 2 of 2	NP_037508.2	Q9UHV2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERTAD1	ENST00000357949.5	TSL:1 MANE Select	c.529A>G	p.Ile177Val	missense	Exon 2 of 2	ENSP00000350633.4	Q9UHV2
	SERTAD1	ENST00000869921.1		c.529A>G	p.Ile177Val	missense	Exon 2 of 2	ENSP00000539980.1
	SERTAD1	ENST00000869922.1		c.529A>G	p.Ile177Val	missense	Exon 2 of 2	ENSP00000539981.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1424870 Hom.: 0 Cov.: 30 AF XY: 0.00000142 AC XY: 1 AN XY: 705550

African (AFR) AF: 0.00 AC: 0 AN: 32608

American (AMR) AF: 0.00 AC: 0 AN: 38774

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25396

East Asian (EAS) AF: 0.00 AC: 0 AN: 37832

South Asian (SAS) AF: 0.00 AC: 0 AN: 82092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50784

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 9.15e-7 AC: 1 AN: 1092664

Other (OTH) AF: 0.00 AC: 0 AN: 58994

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.39	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.3
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.98	D
Vest4		0.28
MutPred		0.53		Gain of catalytic residue at I177 (P = 0.0507)
MVP		0.66
MPC		0.28
ClinPred		0.75	D
GERP RS		5.3
Varity_R		0.23
gMVP		0.30
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

dbSNP: rs2079603707; hg19: chr19-40928925;