20-62309427-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005560.6(LAMA5):c.10997G>A(p.Arg3666Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00253 in 1,584,524 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (48 hom., cov: 29)
  • Exomes 𝑓: 0.0014 (50 hom.)
• Consequence: LAMA5 NM_005560.6 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.27

Genes affected

LAMA5 (HGNC:6485): (laminin subunit alpha 5) This gene encodes one of the vertebrate laminin alpha chains. Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Laminins are composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively) and they form a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains. Each laminin chain is a multidomain protein encoded by a distinct gene. The protein encoded by this gene is the alpha-5 subunit of of laminin-10 (laminin-511), laminin-11 (laminin-521) and laminin-15 (laminin-523). [provided by RefSeq, Jun 2013]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004610598).
• BP6: Variant 20-62309427-C-T is Benign according to our data. Variant chr20-62309427-C-T is described in ClinVar as [Benign]. Clinvar id is 769100.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0128 (1947/152106) while in subpopulation AFR AF= 0.044 (1825/41474). AF 95% confidence interval is 0.0423. There are 48 homozygotes in gnomad4. There are 928 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 48 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMA5	NM_005560.6	c.10997G>A	p.Arg3666Lys	missense_variant	80/80	ENST00000252999.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMA5	ENST00000252999.7	c.10997G>A	p.Arg3666Lys	missense_variant	80/80	1	NM_005560.6	P1
LAMA5	ENST00000370691.6	n.2792G>A		non_coding_transcript_exon_variant	17/17	1
LAMA5	ENST00000495695.1	n.498G>A		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes AF: 0.0128 AC: 1941 AN: 151988 Hom.: 48 Cov.: 29

Gnomad AFR AF: 0.0440

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00609

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00862

GnomAD3 exomes AF: 0.00307 AC: 625 AN: 203722 Hom.: 8 AF XY: 0.00252 AC XY: 284 AN XY: 112484

Gnomad AFR exome AF: 0.0425

Gnomad AMR exome AF: 0.00263

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000148

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000247

Gnomad OTH exome AF: 0.00154

GnomAD4 exome AF: 0.00144 AC: 2063 AN: 1432418 Hom.: 50 Cov.: 32 AF XY: 0.00129 AC XY: 920 AN XY: 711446

Gnomad4 AFR exome AF: 0.0459

Gnomad4 AMR exome AF: 0.00300

Gnomad4 ASJ exome AF: 0.0000390

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000217

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000168

Gnomad4 OTH exome AF: 0.00310

GnomAD4 genome AF: 0.0128 AC: 1947 AN: 152106 Hom.: 48 Cov.: 29 AF XY: 0.0125 AC XY: 928 AN XY: 74342

Gnomad4 AFR AF: 0.0440

Gnomad4 AMR AF: 0.00602

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00853

Alfa AF: 0.00170 Hom.: 2

Bravo AF: 0.0147

ESP6500AA AF: 0.0248 AC: 102

ESP6500EA AF: 0.000244 AC: 2

ExAC AF: 0.00321 AC: 379

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 08, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.26
Cadd	Benign	20
Dann	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.58	T
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-0.40	T
MutationAssessor	Uncertain	2.3	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.55
Sift	Benign	0.50	T
Sift4G	Benign	0.47	T
Polyphen		1.0	D
Vest4		0.53
MVP		0.87
ClinPred		0.046	T
GERP RS		5.4
Varity_R		0.31
gMVP		0.66

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

LitVar

Other links and lift over

dbSNP: rs77172131; hg19: chr20-60884483;