chr5-177496439-T-A

Variant names:

• chr5-177496439-T-A
• rs372976882
• NM_005451.5:c.74A>T

Variant summary

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

The NM_005451.5(PDLIM7):​c.74A>T​(p.Asn25Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. N25S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PDLIM7 NM_005451.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.09
• Publications: 0 publications found

Genes affected

PDLIM7 (HGNC:22958): (PDZ and LIM domain 7) The protein encoded by this gene is representative of a family of proteins composed of conserved PDZ and LIM domains. LIM domains are proposed to function in protein-protein recognition in a variety of contexts including gene transcription and development and in cytoskeletal interaction. The LIM domains of this protein bind to protein kinases, whereas the PDZ domain binds to actin filaments. The gene product is involved in the assembly of an actin filament-associated complex essential for transmission of ret/ptc2 mitogenic signaling. The biological function is likely to be that of an adapter, with the PDZ domain localizing the LIM-binding proteins to actin filaments of both skeletal muscle and nonmuscle tissues. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

PDLIM7-AS1 (HGNC:41004): (PDLIM7 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005451.5. 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
	PDLIM7	NM_005451.5	MANE Select	c.74A>T	p.Asn25Ile	missense	Exon 2 of 13	NP_005442.2
	PDLIM7	NM_203352.3		c.74A>T	p.Asn25Ile	missense	Exon 2 of 13	NP_976227.1	Q9NR12-2
	PDLIM7	NM_213636.3		c.74A>T	p.Asn25Ile	missense	Exon 2 of 8	NP_998801.1	Q9NR12-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDLIM7	ENST00000355841.7	TSL:1 MANE Select	c.74A>T	p.Asn25Ile	missense	Exon 2 of 13	ENSP00000348099.2	Q9NR12-1
	PDLIM7	ENST00000359895.6	TSL:1	c.74A>T	p.Asn25Ile	missense	Exon 2 of 13	ENSP00000352964.2	Q9NR12-2
	PDLIM7	ENST00000393551.5	TSL:1	c.74A>T	p.Asn25Ile	missense	Exon 2 of 9	ENSP00000377182.1	Q9NR12-4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Benign	-0.0011	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.49	T
MutationAssessor	Pathogenic	3.9	H
PhyloP100		2.1
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-6.5	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.98	D
Vest4		0.56
MutPred		0.53		Loss of catalytic residue at N25 (P = 0.0217)
MVP		0.61
MPC		0.89
ClinPred		1.0	D
GERP RS		4.9
PromoterAI		-0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.91
gMVP		0.62
Mutation Taster		=52/48	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs372976882; hg19: chr5-176923440;