chr16-30965819-C-T

Variant names:

• chr16-30965819-C-T
• rs770913157
• NM_014712.3:c.1938C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_014712.3(SETD1A):​c.1938C>T​(p.Tyr646Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000383 in 1,566,862 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: 𝑓 0.000014 (0 hom., cov: 25)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: SETD1A NM_014712.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.695
• Publications: 2 publications found

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]

SETD1A Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with speech impairment and dysmorphic facies

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• epilepsy, early-onset, with or without developmental delay

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=0.695 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014712.3. 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
	SETD1A	NM_014712.3	MANE Select	c.1938C>T	p.Tyr646Tyr	synonymous	Exon 8 of 19	NP_055527.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SETD1A	ENST00000262519.14	TSL:1 MANE Select	c.1938C>T	p.Tyr646Tyr	synonymous	Exon 8 of 19	ENSP00000262519.8
	SETD1A	ENST00000684162.1		c.1938C>T	p.Tyr646Tyr	synonymous	Exon 8 of 19	ENSP00000507683.1
	SETD1A	ENST00000710314.1		c.1938C>T	p.Tyr646Tyr	synonymous	Exon 8 of 19	ENSP00000518195.1

Frequencies

GnomAD3 genomes AF: 0.0000135 AC: 2 AN: 148064 Hom.: 0 Cov.: 25

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: 0.0000299

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000173 AC: 4 AN: 231392 AF XY: 0.0000240

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000282 AC: 4 AN: 1418798 Hom.: 0 Cov.: 45 AF XY: 0.00000426 AC XY: 3 AN XY: 704862

African (AFR) AF: 0.00 AC: 0 AN: 32524

American (AMR) AF: 0.00 AC: 0 AN: 42010

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24438

East Asian (EAS) AF: 0.00 AC: 0 AN: 39120

South Asian (SAS) AF: 0.0000482 AC: 4 AN: 82986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51714

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5608

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1081818

Other (OTH) AF: 0.00 AC: 0 AN: 58580

GnomAD4 genome AF: 0.0000135 AC: 2 AN: 148064 Hom.: 0 Cov.: 25 AF XY: 0.0000139 AC XY: 1 AN XY: 72090

African (AFR) AF: 0.00 AC: 0 AN: 40220

American (AMR) AF: 0.00 AC: 0 AN: 14796

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3438

East Asian (EAS) AF: 0.00 AC: 0 AN: 4904

South Asian (SAS) AF: 0.00 AC: 0 AN: 4534

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9974

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000299 AC: 2 AN: 66962

Other (OTH) AF: 0.00 AC: 0 AN: 2038

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	1.4
DANN	Benign	0.37
PhyloP100		0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs770913157; hg19: chr16-30977140;