9-6328947-T-C

Variant names:

• chr9-6328947-T-C
• rs3847262
• NM_001001874.3:c.352T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001001874.3(TPD52L3):​c.352T>C​(p.Phe118Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.946 in 1,614,118 control chromosomes in the GnomAD database, including 723,971 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.92 (64315 hom., cov: 31)
  • Exomes 𝑓: 0.95 (659656 hom.)
• Consequence: TPD52L3 NM_001001874.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55
• Publications: 28 publications found

Genes affected

TPD52L3 (HGNC:23382): (TPD52 like 3) This gene encodes a member of the tumor protein D52-like family of proteins. These proteins are characterized by an N-terminal coiled-coil motif that is used to form homo- and heteromeric complexes with other tumor protein D52-like proteins. The encoded protein may play a role in spermatogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.4859298E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001874.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPD52L3	NM_001001874.3	MANE Select	c.352T>C	p.Phe118Leu	missense	Exon 1 of 2	NP_001001874.2
	TPD52L3	NM_033516.6		c.352T>C	p.Phe118Leu	missense	Exon 1 of 1	NP_277051.4
	TPD52L3	NM_001001875.4		c.352T>C	p.Phe118Leu	missense	Exon 1 of 2	NP_001001875.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPD52L3	ENST00000314556.4	TSL:1 MANE Select	c.352T>C	p.Phe118Leu	missense	Exon 1 of 2	ENSP00000318665.3
	TPD52L3	ENST00000381428.1	TSL:1	c.352T>C	p.Phe118Leu	missense	Exon 1 of 2	ENSP00000370836.1
	TPD52L3	ENST00000344545.6	TSL:6	c.352T>C	p.Phe118Leu	missense	Exon 1 of 1	ENSP00000341677.5

Frequencies

GnomAD3 genomes AF: 0.917 AC: 139434 AN: 152114 Hom.: 64286 Cov.: 31

Gnomad AFR AF: 0.813

Gnomad AMI AF: 0.954

Gnomad AMR AF: 0.942

Gnomad ASJ AF: 0.961

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.974

Gnomad FIN AF: 0.984

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.950

Gnomad OTH AF: 0.915

GnomAD2 exomes AF: 0.953 AC: 238962 AN: 250698 AF XY: 0.955

Gnomad AFR exome AF: 0.814

Gnomad AMR exome AF: 0.966

Gnomad ASJ exome AF: 0.960

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.982

Gnomad NFE exome AF: 0.952

Gnomad OTH exome AF: 0.953

GnomAD4 exome AF: 0.950 AC: 1388221 AN: 1461886 Hom.: 659656 Cov.: 86 AF XY: 0.951 AC XY: 691382 AN XY: 727242

African (AFR) AF: 0.812 AC: 27178 AN: 33480

American (AMR) AF: 0.963 AC: 43086 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.961 AC: 25107 AN: 26136

East Asian (EAS) AF: 1.00 AC: 39693 AN: 39700

South Asian (SAS) AF: 0.969 AC: 83561 AN: 86258

European-Finnish (FIN) AF: 0.978 AC: 52264 AN: 53420

Middle Eastern (MID) AF: 0.939 AC: 5417 AN: 5766

European-Non Finnish (NFE) AF: 0.949 AC: 1054935 AN: 1112008

Other (OTH) AF: 0.943 AC: 56980 AN: 60394

GnomAD4 genome AF: 0.916 AC: 139515 AN: 152232 Hom.: 64315 Cov.: 31 AF XY: 0.920 AC XY: 68463 AN XY: 74424

African (AFR) AF: 0.813 AC: 33734 AN: 41510

American (AMR) AF: 0.942 AC: 14405 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.961 AC: 3333 AN: 3468

East Asian (EAS) AF: 0.999 AC: 5171 AN: 5174

South Asian (SAS) AF: 0.974 AC: 4704 AN: 4828

European-Finnish (FIN) AF: 0.984 AC: 10442 AN: 10614

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.950 AC: 64651 AN: 68024

Other (OTH) AF: 0.916 AC: 1934 AN: 2112

Alfa AF: 0.937 Hom.: 150632

Bravo AF: 0.910

TwinsUK AF: 0.945 AC: 3503

ALSPAC AF: 0.946 AC: 3646

ESP6500AA AF: 0.825 AC: 3633

ESP6500EA AF: 0.947 AC: 8142

ExAC AF: 0.950 AC: 115315

Asia WGS AF: 0.977 AC: 3397 AN: 3478

EpiCase AF: 0.945

EpiControl AF: 0.950

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.66	T
MetaRNN	Benign	0.0000015	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		1.5
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Benign	0.27
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.050	T
Polyphen		1.0	D
Vest4		0.19
MutPred		0.86		Loss of sheet (P = 0.0228)
MPC		0.024
ClinPred		0.057	T
GERP RS		4.4
Varity_R		0.74
gMVP		0.068
Mutation Taster		=99/1	polymorphism (auto)

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: rs3847262; hg19: chr9-6328947; COSMIC: COSV106447754;