2-27657426-A-T

Position:

• chr2-27657426-A-T

Variant summary

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

The NM_014860.3(SUPT7L):​c.663T>A​(p.His221Gln) variant causes a missense change involving the alteration of a non-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: 32)
• Consequence: SUPT7L NM_014860.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0690

Genes affected

SUPT7L (HGNC:30632): (SPT7 like, STAGA complex subunit gamma) SUPT7L is a protein subunit of the human STAGA complex (SPT3; (MIM 602947)/TAF9 (MIM 600822)/GCN5 (MIM 602301) acetyltransferase complex), which is a chromatin-modifying multiprotein complex (Martinez et al., 2001 [PubMed 11564863]).[supplied by OMIM, Apr 2009]

SUPT7L (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUPT7L	NM_014860.3	c.663T>A	p.His221Gln	missense_variant	4/6	ENST00000337768.10	NP_055675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUPT7L	ENST00000337768.10	c.663T>A	p.His221Gln	missense_variant	4/6	1	NM_014860.3	ENSP00000336750.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 01, 2022

The c.663T>A (p.H221Q) alteration is located in exon 4 (coding exon 3) of the SUPT7L gene. This alteration results from a T to A substitution at nucleotide position 663, causing the histidine (H) at amino acid position 221 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	0.0041	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	8.8
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T;.;.;.;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.90	D;D;.;.;D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.56	D;D;D;D;D
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.5	M;.;.;.;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.8	D;D;D;D;D
REVEL	Benign	0.24
Sift	Benign	0.059	T;D;T;T;T
Sift4G	Uncertain	0.028	D;D;D;D;D
Polyphen		0.82	P;.;P;P;P
Vest4		0.66
MutPred		0.68		Gain of helix (P = 0.0425);.;.;.;.;
MVP		0.48
MPC		0.34
ClinPred		0.97	D
GERP RS		-2.2
Varity_R		0.34
gMVP		0.51

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: chr2-27880293;