NM_014860.3:c.491C>T

Variant names:

• chr2-27657598-G-A
• rs377222033
• NM_014860.3:c.491C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_014860.3(SUPT7L):​c.491C>T​(p.Thr164Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T164R) has been classified 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: 9.89
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.856

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.491C>T	p.Thr164Ile	missense	Exon 4 of 6	NP_055675.1	O94864-1
	SUPT7L	NM_001282729.2		c.491C>T	p.Thr164Ile	missense	Exon 4 of 6	NP_001269658.1	O94864-1
	SUPT7L	NM_001282730.2		c.485C>T	p.Thr162Ile	missense	Exon 4 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.491C>T	p.Thr164Ile	missense	Exon 4 of 6	ENSP00000336750.5	O94864-1
	SUPT7L	ENST00000405491.5	TSL:1	c.485C>T	p.Thr162Ile	missense	Exon 4 of 6	ENSP00000384469.1	O94864-2
	SUPT7L	ENST00000406540.5	TSL:1	c.485C>T	p.Thr162Ile	missense	Exon 3 of 5	ENSP00000385436.1	O94864-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.37
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.60
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0086	T
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.8	L
PhyloP100		9.9
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.40
Sift	Benign	0.14	T
Sift4G	Benign	0.11	T
Polyphen		0.69	P
Vest4		0.91
MutPred		0.71		Loss of catalytic residue at T164 (P = 0.1333)
MVP		0.50
MPC		0.88
ClinPred		0.93	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.24
gMVP		0.64
Mutation Taster		=24/76	disease causing

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: rs377222033; hg19: chr2-27880465;