2-27661048-C-G

Variant names:

• chr2-27661048-C-G
• rs775824239
• NM_014860.3:c.355G>C

Variant summary

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

The NM_014860.3(SUPT7L):​c.355G>C​(p.Asp119His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D119Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SUPT7L NM_014860.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.43
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• lipodystrophy

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia, Ambry Genetics

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_014860.3. 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
	SUPT7L	NM_014860.3	MANE Select	c.355G>C	p.Asp119His	missense	Exon 3 of 6	NP_055675.1	O94864-1
	SUPT7L	NM_001282729.2		c.355G>C	p.Asp119His	missense	Exon 3 of 6	NP_001269658.1	O94864-1
	SUPT7L	NM_001282730.2		c.349G>C	p.Asp117His	missense	Exon 3 of 6	NP_001269659.1	O94864-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUPT7L	ENST00000337768.10	TSL:1 MANE Select	c.355G>C	p.Asp119His	missense	Exon 3 of 6	ENSP00000336750.5	O94864-1
	SUPT7L	ENST00000405491.5	TSL:1	c.349G>C	p.Asp117His	missense	Exon 3 of 6	ENSP00000384469.1	O94864-2
	SUPT7L	ENST00000406540.5	TSL:1	c.349G>C	p.Asp117His	missense	Exon 2 of 5	ENSP00000385436.1	O94864-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461884 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0047	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	1.1	L
PhyloP100		7.4
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.35
Sift	Uncertain	0.012	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.76
MutPred		0.32		Gain of helix (P = 0.0854)
MVP		0.18
MPC		0.97
ClinPred		0.92	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.63
Mutation Taster		=24/76	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs775824239; hg19: chr2-27883915;