rs776629918

Variant names:

• chr6-45014864-T-G
• rs776629918
• NM_003599.4:c.301A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-45014864-T-G
• chr6-45014864-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_003599.4(SUPT3H):​c.301A>C​(p.Met101Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000187 in 1,589,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: SUPT3H NM_003599.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.84
• Publications: 0 publications found

Genes affected

SUPT3H (HGNC:11466): (SPT3 homolog, SAGA and STAGA complex component) Enables transcription coactivator activity. Involved in histone H3 acetylation and histone deubiquitination. Located in nucleoplasm. Part of SAGA complex and transcription factor TFTC complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10565987).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003599.4. 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
	SUPT3H	NM_003599.4	MANE Select	c.301A>C	p.Met101Leu	missense	Exon 5 of 11	NP_003590.1	O75486-1
	SUPT3H	NM_181356.3		c.334A>C	p.Met112Leu	missense	Exon 7 of 13	NP_852001.1	O75486-4
	SUPT3H	NM_001350324.2		c.301A>C	p.Met101Leu	missense	Exon 5 of 12	NP_001337253.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUPT3H	ENST00000371459.6	TSL:1 MANE Select	c.301A>C	p.Met101Leu	missense	Exon 5 of 11	ENSP00000360514.1	O75486-1
	SUPT3H	ENST00000371460.5	TSL:1	c.334A>C	p.Met112Leu	missense	Exon 7 of 13	ENSP00000360515.1	O75486-4
	SUPT3H	ENST00000889037.1		c.355A>C	p.Met119Leu	missense	Exon 6 of 12	ENSP00000559096.1

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152120 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

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: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000597 AC: 14 AN: 234488 AF XY: 0.0000551

Gnomad AFR exome AF: 0.000127

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: 0.000111

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000201 AC: 289 AN: 1437424 Hom.: 0 Cov.: 29 AF XY: 0.000179 AC XY: 128 AN XY: 714350

African (AFR) AF: 0.0000306 AC: 1 AN: 32698

American (AMR) AF: 0.00 AC: 0 AN: 40992

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25480

East Asian (EAS) AF: 0.00 AC: 0 AN: 38724

South Asian (SAS) AF: 0.00 AC: 0 AN: 80670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5614

European-Non Finnish (NFE) AF: 0.000254 AC: 280 AN: 1101720

Other (OTH) AF: 0.000135 AC: 8 AN: 59194

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152120 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74298

African (AFR) AF: 0.0000965 AC: 4 AN: 41444

American (AMR) AF: 0.0000656 AC: 1 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000116 Hom.: 0

Bravo AF: 0.0000491

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000495 AC: 6

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	Benign	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	20
DANN	Benign	0.86
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.026
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.95	T
PhyloP100		2.8
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.20
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.35
MVP		0.26
MPC		0.045
ClinPred		0.070	T
GERP RS		5.9
Varity_R		0.25
gMVP		0.44
Mutation Taster		=82/18	polymorphism

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: rs776629918; hg19: chr6-44982601;