chr11-555317-T-C

Variant names:

• chr11-555317-T-C
• rs143504198
• NM_173573.3:c.1761A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_173573.3(LMNTD2):​c.1761A>G​(p.Glu587Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00782 in 1,418,240 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0085 (12 hom., cov: 31)
  • Exomes 𝑓: 0.0077 (45 hom.)
• Consequence: LMNTD2 NM_173573.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00500
• Publications: 2 publications found

Genes affected

LMNTD2 (HGNC:28561): (lamin tail domain containing 2) Predicted to be a structural constituent of chromatin. Predicted to be involved in regulation of chromatin assembly. Predicted to act upstream of or within positive regulation of mRNA splicing, via spliceosome. Predicted to be active in lamin filament. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-555317-T-C is Benign according to our data. Variant chr11-555317-T-C is described in ClinVar as Benign. ClinVar VariationId is 2641070.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.005 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173573.3. 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
	LMNTD2	NM_173573.3	MANE Select	c.1761A>G	p.Glu587Glu	synonymous	Exon 13 of 14	NP_775844.2	Q8IXW0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMNTD2	ENST00000329451.8	TSL:1 MANE Select	c.1761A>G	p.Glu587Glu	synonymous	Exon 13 of 14	ENSP00000331167.3	Q8IXW0
	LMNTD2	ENST00000469990.1	TSL:1	n.963A>G		non_coding_transcript_exon	Exon 3 of 4
	LMNTD2	ENST00000886189.1		c.1776A>G	p.Glu592Glu	synonymous	Exon 13 of 14	ENSP00000556248.1

Frequencies

GnomAD3 genomes AF: 0.00841 AC: 1275 AN: 151534 Hom.: 12 Cov.: 31

Gnomad AFR AF: 0.00940

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0131

Gnomad ASJ AF: 0.00433

Gnomad EAS AF: 0.000584

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00548

Gnomad MID AF: 0.00323

Gnomad NFE AF: 0.00867

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00588 AC: 493 AN: 83834 AF XY: 0.00577

Gnomad AFR exome AF: 0.00782

Gnomad AMR exome AF: 0.00772

Gnomad ASJ exome AF: 0.00158

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00423

Gnomad NFE exome AF: 0.00700

Gnomad OTH exome AF: 0.00946

GnomAD4 exome AF: 0.00774 AC: 9805 AN: 1266600 Hom.: 45 Cov.: 32 AF XY: 0.00744 AC XY: 4590 AN XY: 616554

African (AFR) AF: 0.00918 AC: 230 AN: 25052

American (AMR) AF: 0.00884 AC: 160 AN: 18102

Ashkenazi Jewish (ASJ) AF: 0.00441 AC: 78 AN: 17696

East Asian (EAS) AF: 0.00 AC: 0 AN: 29702

South Asian (SAS) AF: 0.0000345 AC: 2 AN: 57930

European-Finnish (FIN) AF: 0.00546 AC: 226 AN: 41416

Middle Eastern (MID) AF: 0.000664 AC: 3 AN: 4518

European-Non Finnish (NFE) AF: 0.00855 AC: 8725 AN: 1020472

Other (OTH) AF: 0.00737 AC: 381 AN: 51712

GnomAD4 genome AF: 0.00845 AC: 1282 AN: 151640 Hom.: 12 Cov.: 31 AF XY: 0.00808 AC XY: 599 AN XY: 74142

African (AFR) AF: 0.00954 AC: 393 AN: 41174

American (AMR) AF: 0.0130 AC: 199 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00433 AC: 15 AN: 3468

East Asian (EAS) AF: 0.000586 AC: 3 AN: 5122

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4800

European-Finnish (FIN) AF: 0.00548 AC: 58 AN: 10578

Middle Eastern (MID) AF: 0.00347 AC: 1 AN: 288

European-Non Finnish (NFE) AF: 0.00867 AC: 589 AN: 67916

Other (OTH) AF: 0.0109 AC: 23 AN: 2108

Alfa AF: 0.00707 Hom.: 2

Bravo AF: 0.00956

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.61
PhyloP100		-0.0050
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs143504198; hg19: chr11-555317; COSMIC: COSV54244037; COSMIC: COSV54244037;