18-23713937-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_198129.4(LAMA3):c.312T>C(p.Tyr104=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000532 in 1,613,768 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00038 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00055 (12 hom.)
• Consequence: LAMA3 NM_198129.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.581

Genes affected

LAMA3 (HGNC:6483): (laminin subunit alpha 3) The protein encoded by this gene belongs to the laminin family of secreted molecules. Laminins are heterotrimeric molecules that consist of alpha, beta, and gamma subunits that assemble through a coiled-coil domain. Laminins are essential for formation and function of the basement membrane and have additional functions in regulating cell migration and mechanical signal transduction. This gene encodes an alpha subunit and is responsive to several epithelial-mesenchymal regulators including keratinocyte growth factor, epidermal growth factor and insulin-like growth factor. Mutations in this gene have been identified as the cause of Herlitz type junctional epidermolysis bullosa and laryngoonychocutaneous syndrome. Alternative splicing and alternative promoter usage result in multiple transcript variants. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 18-23713937-T-C is Benign according to our data. Variant chr18-23713937-T-C is described in ClinVar as [Benign]. Clinvar id is 763328.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.581 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000375 (57/151914) while in subpopulation SAS AF= 0.0117 (56/4802). AF 95% confidence interval is 0.00922. There are 0 homozygotes in gnomad4. There are 39 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMA3	NM_198129.4	c.312T>C	p.Tyr104=	synonymous_variant	2/75	ENST00000313654.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMA3	ENST00000313654.14	c.312T>C	p.Tyr104=	synonymous_variant	2/75	1	NM_198129.4	P1
LAMA3	ENST00000399516.7	c.312T>C	p.Tyr104=	synonymous_variant	2/74	1
LAMA3	ENST00000585600.5	c.312T>C	p.Tyr104=	synonymous_variant	2/13	1

Frequencies

GnomAD3 genomes AF: 0.000382 AC: 58 AN: 151796 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0119

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00118 AC: 295 AN: 249540 Hom.: 8 AF XY: 0.00151 AC XY: 204 AN XY: 135388

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00954

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000330

GnomAD4 exome AF: 0.000548 AC: 801 AN: 1461854 Hom.: 12 Cov.: 34 AF XY: 0.000749 AC XY: 545 AN XY: 727224

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00864

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000899

Gnomad4 OTH exome AF: 0.000695

GnomAD4 genome AF: 0.000375 AC: 57 AN: 151914 Hom.: 0 Cov.: 30 AF XY: 0.000525 AC XY: 39 AN XY: 74248

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0117

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000453

Asia WGS AF: 0.00202 AC: 7 AN: 3478

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

Aug 21, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	1.1
Dann	Benign	0.43

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: rs376865778; hg19: chr18-21293901;