3-8537407-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_014583.4(LMCD1):c.354C>T(p.Tyr118=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00882 in 1,606,354 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0061 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0091 (76 hom.)
• Consequence: LMCD1 NM_014583.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.44

Genes affected

LMCD1 (HGNC:6633): (LIM and cysteine rich domains 1) This gene encodes a member of the LIM-domain family of zinc finger proteins. The encoded protein contains an N-terminal cysteine-rich domain and two C-terminal LIM domains. The presence of LIM domains suggests involvement in protein-protein interactions. The protein may act as a co-regulator of transcription along with other transcription factors. Alternate splicing results in multiple transcript variants of this gene. [provided by RefSeq, May 2013]

LMCD1-AS1 (HGNC:44477): (LMCD1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 3-8537407-C-T is Benign according to our data. Variant chr3-8537407-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2653466.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.44 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMCD1	NM_014583.4	c.354C>T	p.Tyr118=	synonymous_variant	3/6	ENST00000157600.8
LMCD1	NM_001278233.2	c.135C>T	p.Tyr45=	synonymous_variant	2/5
LMCD1	NM_001278235.2	c.354C>T	p.Tyr118=	synonymous_variant	3/5
LMCD1	NM_001278234.2	c.51+4582C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMCD1	ENST00000157600.8	c.354C>T	p.Tyr118=	synonymous_variant	3/6	1	NM_014583.4	P1

Frequencies

GnomAD3 genomes AF: 0.00614 AC: 934 AN: 152190 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00229

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00366

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00394

Gnomad FIN AF: 0.00735

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00972

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00715 AC: 1771 AN: 247838 Hom.: 7 AF XY: 0.00746 AC XY: 998 AN XY: 133718

Gnomad AFR exome AF: 0.00154

Gnomad AMR exome AF: 0.00550

Gnomad ASJ exome AF: 0.00504

Gnomad EAS exome AF: 0.000327

Gnomad SAS exome AF: 0.00484

Gnomad FIN exome AF: 0.00756

Gnomad NFE exome AF: 0.0101

Gnomad OTH exome AF: 0.00997

GnomAD4 exome AF: 0.00910 AC: 13238 AN: 1454046 Hom.: 76 Cov.: 31 AF XY: 0.00911 AC XY: 6573 AN XY: 721802

Gnomad4 AFR exome AF: 0.00162

Gnomad4 AMR exome AF: 0.00574

Gnomad4 ASJ exome AF: 0.00538

Gnomad4 EAS exome AF: 0.000152

Gnomad4 SAS exome AF: 0.00492

Gnomad4 FIN exome AF: 0.00728

Gnomad4 NFE exome AF: 0.0104

Gnomad4 OTH exome AF: 0.00751

GnomAD4 genome AF: 0.00613 AC: 934 AN: 152308 Hom.: 6 Cov.: 32 AF XY: 0.00580 AC XY: 432 AN XY: 74464

Gnomad4 AFR AF: 0.00229

Gnomad4 AMR AF: 0.00366

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00394

Gnomad4 FIN AF: 0.00735

Gnomad4 NFE AF: 0.00972

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00855 Hom.: 2

Bravo AF: 0.00619

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

LMCD1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	0.17
Dann	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs139605755; hg19: chr3-8579093;