10-102403972-C-T

Position:

• chr10-102403972-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_002779.5(PSD):​c.2714G>A​(p.Arg905Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00262 in 1,559,544 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0021 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0027 (9 hom.)
• Consequence: PSD NM_002779.5 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.41

Genes affected

PSD (HGNC:9507): (pleckstrin and Sec7 domain containing) This gene encodes a Plekstrin homology and SEC7 domains-containing protein that functions as a guanine nucleotide exchange factor. The encoded protein regulates signal transduction by activating ADP-ribosylation factor 6. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

PSD (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0052475333).
• BP6: Variant 10-102403972-C-T is Benign according to our data. Variant chr10-102403972-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 770767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSD	NM_002779.5	c.2714G>A	p.Arg905Gln	missense_variant	16/17	ENST00000020673.6	NP_002770.3
PSD	NM_001270965.2	c.2714G>A	p.Arg905Gln	missense_variant	17/18		NP_001257894.1
PSD	NM_001270966.2	c.1577G>A	p.Arg526Gln	missense_variant	17/18		NP_001257895.1
PSD	NR_073110.2	n.1006G>A		non_coding_transcript_exon_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSD	ENST00000020673.6	c.2714G>A	p.Arg905Gln	missense_variant	16/17	1	NM_002779.5	ENSP00000020673.5
PSD	ENST00000406432.5	c.2714G>A	p.Arg905Gln	missense_variant	17/18	1		ENSP00000384830.1
PSD	ENST00000611678.4	c.1577G>A	p.Arg526Gln	missense_variant	17/18	1		ENSP00000481250.1

Frequencies

GnomAD3 genomes AF: 0.00206 AC: 314 AN: 152148 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00321

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00162 AC: 271 AN: 167640 Hom.: 0 AF XY: 0.00154 AC XY: 138 AN XY: 89664

Gnomad AFR exome AF: 0.000497

Gnomad AMR exome AF: 0.000803

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00164

Gnomad NFE exome AF: 0.00316

Gnomad OTH exome AF: 0.00129

GnomAD4 exome AF: 0.00268 AC: 3772 AN: 1407278 Hom.: 9 Cov.: 33 AF XY: 0.00254 AC XY: 1768 AN XY: 695986

Gnomad4 AFR exome AF: 0.000495

Gnomad4 AMR exome AF: 0.000721

Gnomad4 ASJ exome AF: 0.0000396

Gnomad4 EAS exome AF: 0.0000271

Gnomad4 SAS exome AF: 0.0000124

Gnomad4 FIN exome AF: 0.00197

Gnomad4 NFE exome AF: 0.00325

Gnomad4 OTH exome AF: 0.00180

GnomAD4 genome AF: 0.00206 AC: 314 AN: 152266 Hom.: 2 Cov.: 33 AF XY: 0.00195 AC XY: 145 AN XY: 74468

Gnomad4 AFR AF: 0.000529

Gnomad4 AMR AF: 0.000915

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.00321

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00230 Hom.: 0

Bravo AF: 0.00205

TwinsUK AF: 0.00243 AC: 9

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.000916 AC: 4

ESP6500EA AF: 0.00292 AC: 25

ExAC AF: 0.00169 AC: 199

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.081	.;T;T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.059	N
LIST_S2	Uncertain	0.91	D;D;.
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.0052	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	.;L;L
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.3	.;N;N
REVEL	Benign	0.031
Sift	Benign	0.12	.;T;T
Sift4G	Benign	0.22	T;D;D
Polyphen		0.35	B;B;B
Vest4		0.29
MVP		0.15
MPC		0.24
ClinPred		0.018	T
GERP RS		2.4
Varity_R		0.098
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs146615059; hg19: chr10-104163729;