1-210241580-G-T

Variant names:

• chr1-210241580-G-T
• rs373437236
• NM_019605.5:c.314G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_019605.5(SERTAD4):​c.314G>T​(p.Arg105Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000724 in 1,380,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R105Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 30)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SERTAD4 NM_019605.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.13
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.893

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019605.5. 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
	SERTAD4	NM_019605.5	MANE Select	c.314G>T	p.Arg105Leu	missense	Exon 4 of 4	NP_062551.1	Q9NUC0
	SERTAD4	NM_001375428.1		c.314G>T	p.Arg105Leu	missense	Exon 4 of 4	NP_001362357.1	Q9NUC0
	SERTAD4	NM_001354173.2		c.291+1972G>T		intron	N/A	NP_001341102.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERTAD4	ENST00000367012.4	TSL:1 MANE Select	c.314G>T	p.Arg105Leu	missense	Exon 4 of 4	ENSP00000355979.3	Q9NUC0
	SERTAD4	ENST00000933764.1		c.314G>T	p.Arg105Leu	missense	Exon 5 of 5	ENSP00000603823.1
	SERTAD4	ENST00000946958.1		c.314G>T	p.Arg105Leu	missense	Exon 4 of 4	ENSP00000617017.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 146096 Hom.: 0 Cov.: 30

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.24e-7 AC: 1 AN: 1380590 Hom.: 0 Cov.: 35 AF XY: 0.00000147 AC XY: 1 AN XY: 679370

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30440

American (AMR) AF: 0.00 AC: 0 AN: 33078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22836

East Asian (EAS) AF: 0.00 AC: 0 AN: 37992

South Asian (SAS) AF: 0.00 AC: 0 AN: 70826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51246

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5054

European-Non Finnish (NFE) AF: 9.33e-7 AC: 1 AN: 1072342

Other (OTH) AF: 0.00 AC: 0 AN: 56776

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 146096 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 70700

African (AFR) AF: 0.00 AC: 0 AN: 38890

American (AMR) AF: 0.00 AC: 0 AN: 14504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3452

East Asian (EAS) AF: 0.00 AC: 0 AN: 5036

South Asian (SAS) AF: 0.00 AC: 0 AN: 4630

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9122

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67240

Other (OTH) AF: 0.00 AC: 0 AN: 2008

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Benign	0.089
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.017	T
MetaRNN	Pathogenic	0.89	D
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		6.1
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Uncertain	0.55
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0070	B
Vest4		0.92
MutPred		0.78		Loss of sheet (P = 0.0457)
MVP		0.66
MPC		0.52
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.79
gMVP		0.85
Mutation Taster		=49/51	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs373437236; hg19: chr1-210414925;