rs750532808

Variant names:

• chr19-40422840-C-A
• rs750532808
• NM_013376.4:c.707G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-40422840-C-A
• chr19-40422840-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013376.4(SERTAD1):​c.707G>T​(p.Arg236Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,441,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. R236H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SERTAD1 NM_013376.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25100398).

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.707G>T	p.Arg236Leu	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.707G>T	p.Arg236Leu	missense	Exon 2 of 2	ENSP00000350633.4	Q9UHV2
	SERTAD1	ENST00000869921.1		c.707G>T	p.Arg236Leu	missense	Exon 2 of 2	ENSP00000539980.1
	SERTAD1	ENST00000869922.1		c.707G>T	p.Arg236Leu	missense	Exon 2 of 2	ENSP00000539981.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1441920 Hom.: 0 Cov.: 29 AF XY: 0.00000140 AC XY: 1 AN XY: 714690

African (AFR) AF: 0.00 AC: 0 AN: 33026

American (AMR) AF: 0.00 AC: 0 AN: 43318

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39350

South Asian (SAS) AF: 0.00 AC: 0 AN: 84032

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52678

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4406

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1100682

Other (OTH) AF: 0.00 AC: 0 AN: 59320

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.091	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.1
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.91	P
Vest4		0.34
MutPred		0.49		Gain of stability (P = 0.0068)
MVP		0.68
MPC		1.1
ClinPred		0.65	D
GERP RS		3.9
Varity_R		0.34
gMVP		0.28
Mutation Taster		=86/14	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: rs750532808; hg19: chr19-40928747;