chr1-210241787-A-C

Variant names:

• chr1-210241787-A-C
• NM_019605.5:c.521A>C

Variant summary

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

The NM_019605.5(SERTAD4):​c.521A>C​(p.Lys174Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SERTAD4 NM_019605.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.35
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.521A>C	p.Lys174Thr	missense	Exon 4 of 4	NP_062551.1	Q9NUC0
	SERTAD4	NM_001375428.1		c.521A>C	p.Lys174Thr	missense	Exon 4 of 4	NP_001362357.1	Q9NUC0
	SERTAD4	NM_001354173.2		c.291+2179A>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.521A>C	p.Lys174Thr	missense	Exon 4 of 4	ENSP00000355979.3	Q9NUC0
	SERTAD4	ENST00000933764.1		c.521A>C	p.Lys174Thr	missense	Exon 5 of 5	ENSP00000603823.1
	SERTAD4	ENST00000946958.1		c.521A>C	p.Lys174Thr	missense	Exon 4 of 4	ENSP00000617017.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	1.1	L
PhyloP100		7.3
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.075	T
Polyphen		1.0	D
Vest4		0.79
MutPred		0.52		Loss of methylation at K174 (P = 0.0089)
MVP		0.13
MPC		0.51
ClinPred		0.96	D
GERP RS		5.5
Varity_R		0.58
gMVP		0.67
Mutation Taster		=63/37	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

hg19: chr1-210415132;