chr8-97277270-C-G

Variant names:

• chr8-97277270-C-G
• rs200734178
• NM_033512.3:c.575G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033512.3(TSPYL5):​c.575G>C​(p.Gly192Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. G192V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: TSPYL5 NM_033512.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.491
• Publications: 0 publications found

Genes affected

TSPYL5 (HGNC:29367): (TSPY like 5) Predicted to enable chromatin binding activity and histone binding activity. Involved in several processes, including cellular response to gamma radiation; positive regulation of protein kinase B signaling; and positive regulation of protein ubiquitination. Predicted to be active in chromatin and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

LOC101927066 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07113546).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033512.3. 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
	TSPYL5	NM_033512.3	MANE Select	c.575G>C	p.Gly192Ala	missense	Exon 1 of 1	NP_277047.2
	LOC101927066	NR_125390.1		n.471+141800G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPYL5	ENST00000322128.5	TSL:6 MANE Select	c.575G>C	p.Gly192Ala	missense	Exon 1 of 1	ENSP00000322802.3	Q86VY4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251056 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461650 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727114

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111884

Other (OTH) AF: 0.0000331 AC: 2 AN: 60386

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	15
DANN	Benign	0.80
DEOGEN2	Benign	0.0095	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.49
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.024
Sift	Benign	0.14	T
Sift4G	Benign	0.28	T
Polyphen		0.011	B
Vest4		0.11
MutPred		0.28		Gain of helix (P = 0.0854)
MVP		0.20
MPC		0.69
ClinPred		0.096	T
GERP RS		3.3
Varity_R		0.10
gMVP		0.35
Mutation Taster		=94/6	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: rs200734178; hg19: chr8-98289498;