1-210241813-T-C

Variant names:

• chr1-210241813-T-C
• rs146325918
• NM_019605.5:c.547T>C

Variant summary

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

The NM_019605.5(SERTAD4):​c.547T>C​(p.Cys183Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. C183S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SERTAD4 NM_019605.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10657644).

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.547T>C	p.Cys183Arg	missense	Exon 4 of 4	NP_062551.1	Q9NUC0
	SERTAD4	NM_001375428.1		c.547T>C	p.Cys183Arg	missense	Exon 4 of 4	NP_001362357.1	Q9NUC0
	SERTAD4	NM_001354173.2		c.291+2205T>C		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.547T>C	p.Cys183Arg	missense	Exon 4 of 4	ENSP00000355979.3	Q9NUC0
	SERTAD4	ENST00000933764.1		c.547T>C	p.Cys183Arg	missense	Exon 5 of 5	ENSP00000603823.1
	SERTAD4	ENST00000946958.1		c.547T>C	p.Cys183Arg	missense	Exon 4 of 4	ENSP00000617017.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461890 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.00064	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.015	T
Eigen	Benign	0.044
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.93	D
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		1.8
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.063
Sift	Benign	0.099	T
Sift4G	Benign	0.32	T
Polyphen		0.55	P
Vest4		0.20
MutPred		0.37		Gain of disorder (P = 0.0251)
MVP		0.068
MPC		0.15
ClinPred		0.37	T
GERP RS		5.5
Varity_R		0.42
gMVP		0.48
Mutation Taster		=85/15	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: rs146325918; hg19: chr1-210415158;