11-104037183-G-T

Variant names:

• chr11-104037183-G-T
• NM_001001711.3:c.361G>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001001711.3(DDI1):​c.361G>T​(p.Ala121Ser) 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DDI1 NM_001001711.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.159

Genes affected

DDI1 (HGNC:18961): (DNA damage inducible 1 homolog 1) Predicted to enable aspartic-type endopeptidase activity. Involved in several processes, including cellular response to hydroxyurea; proteasomal protein catabolic process; and regulation of DNA stability. [provided by Alliance of Genome Resources, Apr 2022]

PDGFD (HGNC:30620): (platelet derived growth factor D) The protein encoded by this gene is a member of the platelet-derived growth factor family. The four members of this family are mitogenic factors for cells of mesenchymal origin and are characterized by a core motif of eight cysteines, seven of which are found in this factor. This gene product only forms homodimers and, therefore, does not dimerize with the other three family members. It differs from alpha and beta members of this family in having an unusual N-terminal domain, the CUB domain. Two splice variants have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03204292).
• BP6: Variant 11-104037183-G-T is Benign according to our data. Variant chr11-104037183-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3080739.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDI1	NM_001001711.3	c.361G>T	p.Ala121Ser	missense_variant	Exon 1 of 1	ENST00000302259.5	NP_001001711.1
PDGFD	NM_025208.5	c.125-36928C>A		intron_variant	Intron 1 of 6	ENST00000393158.7	NP_079484.1
PDGFD	NM_033135.4	c.125-36946C>A		intron_variant	Intron 1 of 6		NP_149126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDI1	ENST00000302259.5	c.361G>T	p.Ala121Ser	missense_variant	Exon 1 of 1	6	NM_001001711.3	ENSP00000302805.3
PDGFD	ENST00000393158.7	c.125-36928C>A		intron_variant	Intron 1 of 6	1	NM_025208.5	ENSP00000376865.2
PDGFD	ENST00000302251.9	c.125-36946C>A		intron_variant	Intron 1 of 6	1		ENSP00000302193.5
PDGFD	ENST00000529268.1	c.-157C>A		upstream_gene_variant		5		ENSP00000432909.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 03, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.014
DANN	Benign	0.55
DEOGEN2	Benign	0.0010	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-2.4	N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.14	N
REVEL	Benign	0.0060
Sift	Benign	0.99	T
Sift4G	Benign	0.98	T
Polyphen		0.0	B
Vest4		0.070
MutPred		0.18		Gain of phosphorylation at A121 (P = 0.0205);
MVP		0.17
MPC		0.35
ClinPred		0.067	T
GERP RS		-5.5
Varity_R		0.037
gMVP		0.26

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: chr11-103907911;