9-35616039-T-A

Position:

• chr9-35616039-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001782.3(CD72):​c.592A>T​(p.Thr198Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CD72 NM_001782.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.124

Genes affected

CD72 (HGNC:1696): (CD72 molecule) Predicted to enable signaling receptor binding activity. Predicted to be involved in cell adhesion. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03412357).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD72	NM_001782.3	c.592A>T	p.Thr198Ser	missense_variant	5/9	ENST00000259633.9	NP_001773.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD72	ENST00000259633.9	c.592A>T	p.Thr198Ser	missense_variant	5/9	1	NM_001782.3	ENSP00000259633	P1
CD72	ENST00000490239.5	n.973A>T		non_coding_transcript_exon_variant	4/8	1
CD72	ENST00000463720.5	n.700A>T		non_coding_transcript_exon_variant	5/5	3
CD72	ENST00000477364.5	n.594A>T		non_coding_transcript_exon_variant	5/5	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.592A>T (p.T198S) alteration is located in exon 5 (coding exon 5) of the CD72 gene. This alteration results from a A to T substitution at nucleotide position 592, causing the threonine (T) at amino acid position 198 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.39
DANN	Benign	0.38
DEOGEN2	Benign	0.082	T;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.43	.;T;T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.034	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;L;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.060	N;N;.
REVEL	Benign	0.015
Sift	Benign	0.29	T;T;.
Sift4G	Benign	0.63	T;T;T
Polyphen		0.016	B;B;.
Vest4		0.061
MutPred		0.28		Gain of phosphorylation at T198 (P = 0.0769);Gain of phosphorylation at T198 (P = 0.0769);Gain of phosphorylation at T198 (P = 0.0769);
MVP		0.30
MPC		0.21
ClinPred		0.053	T
GERP RS		-1.4
Varity_R		0.030
gMVP		0.061

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-35616036;