17-44014899-C-T

Variant names:

• chr17-44014899-C-T
• rs35301047
• NM_032376.4:c.54G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_032376.4(TMEM101):​c.54G>A​(p.Leu18Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00865 in 1,614,028 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (16 hom., cov: 33)
  • Exomes 𝑓: 0.0083 (72 hom.)
• Consequence: TMEM101 NM_032376.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.02
• Publications: 5 publications found

Genes affected

TMEM101 (HGNC:28653): (transmembrane protein 101) Involved in positive regulation of I-kappaB kinase/NF-kappaB signaling. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000305936 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 17-44014899-C-T is Benign according to our data. Variant chr17-44014899-C-T is described in ClinVar as Benign. ClinVar VariationId is 774518.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.02 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0121 (1850/152378) while in subpopulation AFR AF = 0.0279 (1160/41582). AF 95% confidence interval is 0.0266. There are 16 homozygotes in GnomAd4. There are 885 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 16 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032376.4. 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
	TMEM101	NM_032376.4	MANE Select	c.54G>A	p.Leu18Leu	synonymous	Exon 1 of 4	NP_115752.1	Q96IK0
	TMEM101	NM_001304813.2		c.-38+85G>A		intron	N/A	NP_001291742.1	B4DFS4
	TMEM101	NM_001304814.2		c.-38+85G>A		intron	N/A	NP_001291743.1	B4DFS4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM101	ENST00000206380.8	TSL:1 MANE Select	c.54G>A	p.Leu18Leu	synonymous	Exon 1 of 4	ENSP00000206380.3	Q96IK0
	TMEM101	ENST00000589334.5	TSL:5	c.54G>A	p.Leu18Leu	synonymous	Exon 2 of 5	ENSP00000468025.1	Q96IK0
	TMEM101	ENST00000860792.1		c.54G>A	p.Leu18Leu	synonymous	Exon 1 of 4	ENSP00000530851.1

Frequencies

GnomAD3 genomes AF: 0.0121 AC: 1846 AN: 152260 Hom.: 16 Cov.: 33

Gnomad AFR AF: 0.0279

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00896

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.000470

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00769

Gnomad OTH AF: 0.00860

GnomAD2 exomes AF: 0.00602 AC: 1512 AN: 251160 AF XY: 0.00528

Gnomad AFR exome AF: 0.0267

Gnomad AMR exome AF: 0.00617

Gnomad ASJ exome AF: 0.000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000370

Gnomad NFE exome AF: 0.00711

Gnomad OTH exome AF: 0.00458

GnomAD4 exome AF: 0.00829 AC: 12116 AN: 1461650 Hom.: 72 Cov.: 31 AF XY: 0.00779 AC XY: 5661 AN XY: 727162

African (AFR) AF: 0.0302 AC: 1011 AN: 33464

American (AMR) AF: 0.00640 AC: 286 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00119 AC: 31 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39688

South Asian (SAS) AF: 0.000313 AC: 27 AN: 86234

European-Finnish (FIN) AF: 0.000374 AC: 20 AN: 53412

Middle Eastern (MID) AF: 0.00260 AC: 15 AN: 5766

European-Non Finnish (NFE) AF: 0.00911 AC: 10132 AN: 1111888

Other (OTH) AF: 0.00982 AC: 593 AN: 60384

GnomAD4 genome AF: 0.0121 AC: 1850 AN: 152378 Hom.: 16 Cov.: 33 AF XY: 0.0119 AC XY: 885 AN XY: 74518

African (AFR) AF: 0.0279 AC: 1160 AN: 41582

American (AMR) AF: 0.00895 AC: 137 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4834

European-Finnish (FIN) AF: 0.000470 AC: 5 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00769 AC: 523 AN: 68044

Other (OTH) AF: 0.00851 AC: 18 AN: 2116

Alfa AF: 0.0102 Hom.: 8

Bravo AF: 0.0145

Asia WGS AF: 0.00173 AC: 7 AN: 3478

EpiCase AF: 0.00938

EpiControl AF: 0.00824

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.87
PhyloP100		2.0
PromoterAI		0.055	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs35301047; hg19: chr17-42092267; COSMIC: COSV99243944;