rs138575873

Variant names:

• chr21-36038182-A-C
• rs138575873
• NM_017438.5:c.1156T>G

Your query was ambiguous. Multiple possible variants found:

• chr21-36038182-A-C
• chr21-36038182-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017438.5(SETD4):​c.1156T>G​(p.Phe386Val) 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 1,461,704 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. F386I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SETD4 NM_017438.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76

Genes affected

SETD4 (HGNC:1258): (SET domain containing 4) Enables histone methyltransferase activity (H4-K20 specific). Involved in histone H4-K20 trimethylation. Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07741979).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SETD4	NM_017438.5	c.1156T>G	p.Phe386Val	missense_variant	Exon 10 of 12	ENST00000332131.9	NP_059134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SETD4	ENST00000332131.9	c.1156T>G	p.Phe386Val	missense_variant	Exon 10 of 12	2	NM_017438.5	ENSP00000329189.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251234 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135782

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461704 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727136

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.017	T;.;T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.46
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.68	.;T;T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.077	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	M;.;M
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.51	N;N;N
REVEL	Benign	0.054
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.17	T;.;T
Polyphen		0.0050	B;B;B
Vest4		0.39
MutPred		0.50		Gain of helix (P = 0.027);.;Gain of helix (P = 0.027);
MVP		0.18
MPC		0.25
ClinPred		0.098	T
GERP RS		2.1
Varity_R		0.045
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs138575873; hg19: chr21-37410480;