rs869312831

Variant names:

• chr16-30966090-C-A
• NM_014712.3:c.2209C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-30966090-C-A
• chr16-30966090-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014712.3(SETD1A):​c.2209C>A​(p.Gln737Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000695 in 1,439,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SETD1A NM_014712.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.79

Genes affected

SETD1A (HGNC:29010): (SET domain containing 1A, histone lysine methyltransferase) The protein encoded by this gene is a component of a histone methyltransferase (HMT) complex that produces mono-, di-, and trimethylated histone H3 at Lys4. Trimethylation of histone H3 at lysine 4 (H3K4me3) is a chromatin modification known to generally mark the transcription start sites of active genes. The protein contains SET domains, a RNA recognition motif domain and is a member of the class V-like SAM-binding methyltransferase superfamily. [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37393847).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SETD1A	NM_014712.3	c.2209C>A	p.Gln737Lys	missense_variant	Exon 8 of 19	ENST00000262519.14	NP_055527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SETD1A	ENST00000262519.14	c.2209C>A	p.Gln737Lys	missense_variant	Exon 8 of 19	1	NM_014712.3	ENSP00000262519.8
SETD1A	ENST00000684162.1	c.2209C>A	p.Gln737Lys	missense_variant	Exon 8 of 19			ENSP00000507683.1
SETD1A	ENST00000710314.1	c.2209C>A	p.Gln737Lys	missense_variant	Exon 8 of 19			ENSP00000518195.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1439642 Hom.: 0 Cov.: 38 AF XY: 0.00000140 AC XY: 1 AN XY: 713450

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.10e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.034	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.37	T
MetaSVM	Uncertain	0.37	D
MutationAssessor	Benign	1.4	L
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.38
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.17	T
Polyphen		0.82	P
Vest4		0.54
MutPred		0.34		Gain of methylation at Q737 (P = 0.002);
MVP		0.75
MPC		0.44
ClinPred		0.63	D
GERP RS		5.6
Varity_R		0.29
gMVP		0.50

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-30977411;